Medical Sciences Commons^™

G Protein Βγ Subunits Regulate Cardiomyocyte Hypertrophy Through A Perinuclear Golgi Phosphatidylinositol 4-Phosphate Hydrolysis Pathway., S Malik, R G Derubio, M Trembley, R Irannejad, Philip B Wedegaertner, A V Smrcka

Department of Biochemistry and Molecular Biology Faculty Papers

We recently identified a novel GPCR-dependent pathway for regulation of cardiac hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P) hydrolysis by a specific isoform of phospholipase C (PLC), PLCε, at the nuclear envelope. How stimuli are transmitted from cell surface GPCRs to activation of perinuclear PLCε is not clear. Here we tested the role of G protein βγ subunits. Gβγ inhibition blocked ET-1-stimulated Golgi PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gβγ at the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation. Translocation of Gβγ to the Golgi stimulated perinuclear Golgi PI4P depletion and nuclear PKD activation. …

Diversification Of Importin-Α Isoforms In Cellular Trafficking And Disease States., Ruth A. Pumroy, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific …

Disrupting Sumoylation Enhances Transcriptional Function And Ameliorates Polyglutamine Androgen Receptor-Mediated Disease., Jason P Chua, Satya L Reddy, Zhigang Yu, Elisa Giorgetti, Heather L Montie, Sarmistha Mukherjee, Jake Higgins, Richard C Mceachin, Diane M Robins, Diane E Merry, Jorge A Iñiguez-Lluhí, Andrew P Lieberman

Department of Biochemistry and Molecular Biology Faculty Papers

Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes neuromuscular degeneration in individuals with spinobulbar muscular atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits ligand-dependent proteotoxicity, features that have both been implicated in SBMA; however, the extent to which altered AR transcriptional function contributes to pathogenesis remains controversial. Here, we sought to dissociate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcriptional activity of polyQ AR. To accomplish this, we bypassed the inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like modifier) by mutating conserved lysines in the polyQ AR that …

Oligomerization, Conformational Stability And Thermal Unfolding Of Harpin, Hrpzpss And Its Hypersensitive Response-Inducing C-Terminal Fragment, C-214-Hrpzpss., Pradip K Tarafdar, Lakshmi Vasudev Vedantam, Rajeshwer S Sankhala, Pallinti Purushotham, Appa Rao Podile, Musti J Swamy

Department of Biochemistry and Molecular Biology Faculty Papers

HrpZ-a harpin from Pseudomonas syringae-is a highly thermostable protein that exhibits multifunctional abilities e.g., it elicits hypersensitive response (HR), enhances plant growth, acts as a virulence factor, and forms pores in plant plasma membranes as well as artificial membranes. However, the molecular mechanism of its biological activity and high thermal stability remained poorly understood. HR inducing abilities of non-overlapping short deletion mutants of harpins put further constraints on the ability to establish structure-activity relationships. We characterized HrpZPss from Pseudomonas syringae pv. syringae and its HR inducing C-terminal fragment with 214 amino acids (C-214-HrpZPss) using calorimetric, spectroscopic and microscopic approaches. Both …

The Regulator Of G Protein Signaling (Rgs) Domain Of G Protein-Coupled Receptor Kinase 5 (Grk5) Regulates Plasma Membrane Localization And Function., Hua Xu, Xiaoshan Jiang, Ke Shen, Christopher C. Fischer, Philip B Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

The G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated GPCRs at the plasma membrane (PM). Here GRK5/GRK4 chimeras and point mutations in GRK5 identify a short sequence within the regulator of G protein signaling (RGS) domain in GRK5 that is critical for GRK5 PM localization. This region of the RGS domain of GRK5 coincides with a region of GRK6 and GRK1 shown to form a hydrophobic dimeric interface (HDI) in crystal structures. Coimmunoprecipitation (coIP) and acceptor photobleaching fluorescence resonance energy transfer assays show that expressed GRK5 self-associates in cells, whereas GRK5-M165E/F166E (GRK5-EE), containing hydrophilic mutations in the HDI region of …

Amino Acid-Dependent Stability Of The Acyl Linkage In Aminoacyl-Trna., Jacob R Peacock, Ryan R Walvoord, Angela Y Chang, Marisa C Kozlowski, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacyl-tRNAs are the biologically active substrates for peptide bond formation in protein synthesis. The stability of the acyl linkage in each aminoacyl-tRNA, formed through an ester bond that connects the amino acid carboxyl group with the tRNA terminal 3'-OH group, is thus important. While the ester linkage is the same for all aminoacyl-tRNAs, the stability of each is not well characterized, thus limiting insight into the fundamental process of peptide bond formation. Here, we show, by analysis of the half-lives of 12 of the 22 natural aminoacyl-tRNAs used in peptide bond formation, that the stability of the acyl linkage is …

Architecture Of Viral Genome-Delivery Molecular Machines., Anshul Bhardwaj, Adam S. Olia, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

From the abyss of the ocean to the human gut, bacterial viruses (or bacteriophages) have colonized all ecosystems of the planet earth and evolved in sync with their bacterial hosts. Over 95% of bacteriophages have a tail that varies greatly in length and complexity. The tail complex interrupts the icosahedral capsid symmetry and provides both an entry for viral genome-packaging during replication and an exit for genome-ejection during infection. Here, we review recent progress in deciphering the structure, assembly and conformational dynamics of viral genome-delivery tail machines. We focus on the bacteriophages P22 and T7, two well-studied members of the …

Exploring The Atomic Structure And Conformational Flexibility Of A 320 Å Long Engineered Viral Fiber Using X-Ray Crystallography., Anshul Bhardwaj, Sherwood R Casjens, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Protein fibers are widespread in nature, but only a limited number of high-resolution structures have been determined experimentally. Unlike globular proteins, fibers are usually recalcitrant to form three-dimensional crystals, preventing single-crystal X-ray diffraction analysis. In the absence of three-dimensional crystals, X-ray fiber diffraction is a powerful tool to determine the internal symmetry of a fiber, but it rarely yields atomic resolution structural information on complex protein fibers. An 85-residue-long minimal coiled-coil repeat unit (MiCRU) was previously identified in the trimeric helical core of tail needle gp26, a fibrous protein emanating from the tail apparatus of the bacteriophage P22 virion. Here, …

Conservation Of Structure And Mechanism By Trm5 Enzymes., Thomas Christian, Howard Gamper, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Enzymes of the Trm5 family catalyze methyl transfer from S-adenosyl methionine (AdoMet) to the N¹ of G37 to synthesize m¹ G37-tRNA as a critical determinant to prevent ribosome frameshift errors. Trm5 is specific to eukaryotes and archaea, and it is unrelated in evolution from the bacterial counterpart TrmD, which is a leading anti-bacterial target. The successful targeting of TrmD requires detailed information on Trm5 to avoid cross-species inhibition. However, most information on Trm5 is derived from studies of the archaeal enzyme Methanococcus jannaschii (MjTrm5), whereas little information is available for eukaryotic enzymes. Here we use human Trm5 (Homo sapiens; HsTrm5) …

Regulation Of Cell Death By Transfer Rna., Ya-Ming Hou, Xiaolu Yang

Department of Biochemistry and Molecular Biology Faculty Papers

SIGNIFICANCE: Both transfer RNA (tRNA) and cytochrome c are essential molecules for the survival of cells. tRNA decodes mRNA codons into amino-acid-building blocks in protein in all organisms, whereas cytochrome c functions in the electron transport chain that powers ATP synthesis in mitochondrion-containing eukaryotes. Additionally, in vertebrates, cytochrome c that is released from mitochondria is a potent inducer of apoptosis, activating apoptotic proteins (caspases) in the cytoplasm to dismantle cells. A better understanding of both tRNA and cytochrome c is essential for an insight into the regulation of cell life and death.

RECENT ADVANCES: A recent study showed that the …

Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …

The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., Justin C Leavitt, Lasha Gogokhia, Eddie B Gilcrease, Anshul Bhardwaj, Gino Cingolani, Sherwood R Casjens

Department of Biochemistry and Molecular Biology Faculty Papers

The P22-like bacteriophages have short tails. Their virions bind to their polysaccharide receptors through six trimeric tailspike proteins that surround the tail tip. These short tails also have a trimeric needle protein that extends beyond the tailspikes from the center of the tail tip, in a position that suggests that it should make first contact with the host's outer membrane during the infection process. The base of the needle serves as a plug that keeps the DNA in the virion, but role of the needle during adsorption and DNA injection is not well understood. Among the P22-like phages are needle …

Dynein And Dynactin Leverage Their Bivalent Character To Form A High-Affinity Interaction., Amanda E Siglin, Shangjin Sun, Jeffrey K Moore, Sarah Tan, Martin Poenie, James D Lear, Tatyana Polenova, John A Cooper, John C Williams

Department of Biochemistry and Molecular Biology Faculty Papers

Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC) and the dynactin p150(Glued); however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10-44, is sufficient for binding p150(Glued). Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, …

Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas

Department of Biochemistry and Molecular Biology Faculty Papers

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr …

Molecular Determinants Of Epidermal Growth Factor Binding: A Molecular Dynamics Study., Jeffrey M Sanders, Matthew E Wampole, Mathew L. Thakur, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family that plays a role in multiple cellular processes. Activation of EGFR requires binding of a ligand on the extracellular domain to promote conformational changes leading to dimerization and transphosphorylation of intracellular kinase domains. Seven ligands are known to bind EGFR with affinities ranging from sub-nanomolar to near micromolar dissociation constants. In the case of EGFR, distinct conformational states assumed upon binding a ligand is thought to be a determining factor in activation of a downstream signaling network. Previous biochemical studies suggest the existence of both …

Structural Implications For Selective Targeting Of Parps., Jamin D Steffen, Md, Jonathan Brody, Md, Roger S Armen, Md, John M Pascal, Md

Department of Biochemistry and Molecular Biology Faculty Papers

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents …

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …

Global Cellular Regulation Including Cardiac Function By Post-Translational Protein Arginylation., Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

In this issue a very significant contribution to cardiology describing critical roles of ATE1 appears by Kurosaka et al. [1]. In view of this paper, as the discoverers of ATE1, we have been asked to contribute an article (editorial) regarding ATE1 (enzyme which transfers arginine from arginyl tRNA to protein acceptors). This short article consists of three sections: 1) a historical anecdote describing how ATE1 was discovered; 2) its possible role in aging and cellular transformation, and most importantly; 3) its role in the development and maintenance of cardiac activity. The last section has direct bearing to the Kurosaka …

Engrailed Cooperates Directly With Extradenticle And Homothorax On A Distinct Class Of Homeodomain Binding Sites To Repress Sloppy Paired., Miki Fujioka, Brian Gebelein, Zenobia C Cofer, Richard S Mann, James B Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Even skipped (Eve) and Engrailed (En) are homeodomain-containing transcriptional repressors with similar DNA binding specificities that are sequentially expressed in Drosophila embryos. The sloppy-paired (slp) locus is a target of repression by both Eve and En. At blastoderm, Eve is expressed in 7 stripes that restrict the posterior border of slp stripes, allowing engrailed (en) gene expression to be initiated in odd-numbered parasegments. En, in turn, prevents expansion of slp stripes after Eve is turned off. Prior studies showed that the two tandem slp transcription units are regulated by cis-regulatory modules (CRMs) with activities that overlap in space and time. …

Protein Synthesis Factors (Rf1, Rf2, Rf3, Rrf, And Tmrna) And Peptidyl-Trna Hydrolase Rescue Stalled Ribosomes At Sense Codons., Serafín Vivanco-Domínguez, José Bueno-Martínez, Gloria León-Avila, Nobuhiro Iwakura, Akira Kaji, Hideko Kaji, Gabriel Guarneros

Department of Biochemistry and Molecular Biology Faculty Papers

During translation, ribosomes stall on mRNA when the aminoacyl-tRNA to be read is not readily available. The stalled ribosomes are deleterious to the cell and should be rescued to maintain its viability. To investigate the contribution of some of the cellular translation factors on ribosome rescuing, we provoked stalling at AGA codons in mutants that affected the factors and then analyzed the accumulation of oligopeptidyl (peptides of up to 6 amino acid residues, oligopep-)-tRNA or polypeptidyl (peptides of more than 300 amino acids in length, polypep-)-tRNA associated with ribosomes. Stalling was achieved by starvation for aminoacyl-tRNA(Arg4) upon induced expression of …

Structural Insights Into Initial And Intermediate Steps Of The Ribosome-Recycling Process, Takeshi Yokoyama, Tanvir R. Shaikh, Nobuhiro Iwakura, Hideko Kaji, Akira Kaji, Rajendra K. Agrawal

Department of Biochemistry and Molecular Biology Faculty Papers

The ribosome recycling factor (RRF) and elongation factor G (EF-G) disassemble the 70S post-termination complex (PoTC) into mRNA, tRNA, and two ribosomal subunits. We have determined cryo-EM structures of the PoTC•RRF complex, with and without EF-G. We find that domain II of RRF initially interacts with universally conserved residues of the 23S rRNA helices 43 and 95, and protein L11 within the 50S ribosomal subunit. Upon EF-G binding, both RRF and tRNA are driven toward the tRNA-exit (E) site, with a large rotational movement of domain II of RRF toward the 30S ribosomal subunit. During this intermediate step of the …

Regulation Of A Duplicated Locus: Drosophila Sloppy Paired Is Replete With Functionally Overlapping Enhancers., Miki Fujioka, James B Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

In order to investigate regulation and redundancy within the sloppy paired (slp) locus, we analyzed 30 kilobases of DNA encompassing the tandem, coordinately regulated slp1 and slp2 transcription units. We found a remarkable array of stripe enhancers with overlapping activities surrounding the slp1 transcription unit, and, unexpectedly, glial cell enhancers surrounding slp2. The slp stripe regulatory region generates 7 stripes at blastoderm, and later 14 stripes that persist throughout embryogenesis. Phylogenetic analysis among drosophilids suggests that the multiplicity of stripe enhancers did not evolve through recent duplication. Most of the direct integration among cis-regulatory modules appears to be simply additive, …

Synergetic Effect Of Recoverin And Calmodulin On Regulation Of Rhodopsin Kinase., Ilya I Grigoriev, Ivan I Senin, Natalya K Tikhomirova, Konstantin E Komolov, Sergei E Permyakov, Evgeni Yu Zernii, Karl-Wilhelm Koch, Pavel P Philippov

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation of photoactivated rhodopsin by rhodopsin kinase (RK or GRK1), a first step of the phototransduction cascade turnoff, is under the control of Ca(2+)/recoverin. Here, we demonstrate that calmodulin, a ubiquitous Ca(2+)-sensor, can inhibit RK, though less effectively than recoverin does. We have utilized the surface plasmon resonance technology to map the calmodulin binding site in the RK molecule. Calmodulin does not interact with the recoverin-binding site within amino acid residues M1-S25 of the enzyme. Instead, the high affinity calmodulin binding site is localized within a stretch of amino acid residues V150-K175 in the N-terminal regulatory region of RK. Moreover, …

Testosterone Treatment Fails To Accelerate Disease In A Transgenic Mouse Model Of Spinal And Bulbar Muscular Atrophy., Erica S Chevalier-Larsen, Diane E Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Evidence from multiple animal models demonstrates that testosterone plays a crucial role in the progression of symptoms in spinal and bulbar muscular atrophy (SBMA), a condition that results in neurodegeneration and muscle atrophy in affected men. Mice bearing a transgene encoding a human androgen receptor (AR) that contains a stretch of 112 glutamines (expanded polyglutamine tract; AR112Q mice) reproduce several aspects of the human disease. We treated transgenic male AR112Q mice with testosterone for 6 months. Surprisingly, testosterone treatment of AR112Q males did not exacerbate the disease. Although transgenic AR112Q males exhibited functional deficits when compared with non-transgenics, long-term testosterone …

Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present …

Structure Of The Atp Synthase Catalytic Complex (F(1)) From Escherichia Coli In An Autoinhibited Conformation., Gino Cingolani, Thomas M Duncan

Department of Biochemistry and Molecular Biology Faculty Papers

ATP synthase is a membrane-bound rotary motor enzyme that is critical for cellular energy metabolism in all kingdoms of life. Despite conservation of its basic structure and function, autoinhibition by one of its rotary stalk subunits occurs in bacteria and chloroplasts but not in mitochondria. The crystal structure of the ATP synthase catalytic complex (F(1)) from Escherichia coli described here reveals the structural basis for this inhibition. The C-terminal domain of subunit ɛ adopts a heretofore unknown, highly extended conformation that inserts deeply into the central cavity of the enzyme and engages both rotor and stator subunits in extensive contacts …

Three Dimensional Projection Environment For Molecular Design And Surgical Simulation, Matthew Wampole, Eric Wickstrom, Chang-Po Chen, Devakumar Devadhas, Yuan-Yuan Jin, Jeffrey M. Sanders, John C. Kairys, Martha L. Ankeny, Rui Hu, Kenneth E. Barner, Karl V. Steiner, Mathew L. Thakur

Department of Biochemistry and Molecular Biology Faculty Papers

Poster presented at "Medicine Meets Virtual Reality" conference February 8-12, 2011 in Newport Beach, California.

Conclusions:

Turning 2D CT/PET slices into 3D objects assists in understanding the topology surrounding tumor masses. Incorporating the visual and physical characteristics of a patient’s anatomy will provide surgeons with an informative pre-operative tool to plan and practice the operation before the first incision. Including haptic feedback provides a familiar 'feel' to surgeons as they palpate the target organ, trying to locate the tumor and determine how large a margin of resection will be needed. The development of genetic PET imaging and contrast CT into …

Mitochondrial Genome Sequence Analysis: A Custom Bioinformatics Pipeline Substantially Improves Affymetrix Mitochip V2.0 Call Rate And Accuracy., Hongbo M Xie, Juan C Perin, Theodore G Schurr, Matthew C Dulik, Sergey I Zhadanov, Joseph A Baur, Michael P King, Emily Place, Colleen Clarke, Michael Grauer, Jonathan Schug, Avni Santani, Anthony Albano, Cecilia Kim, Vincent Procaccio, Hakon Hakonarson, Xiaowu Gai, Marni J Falk

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Mitochondrial genome sequence analysis is critical to the diagnostic evaluation of mitochondrial disease. Existing methodologies differ widely in throughput, complexity, cost efficiency, and sensitivity of heteroplasmy detection. Affymetrix MitoChip v2.0, which uses a sequencing-by-genotyping technology, allows potentially accurate and high-throughput sequencing of the entire human mitochondrial genome to be completed in a cost-effective fashion. However, the relatively low call rate achieved using existing software tools has limited the wide adoption of this platform for either clinical or research applications. Here, we report the design and development of a custom bioinformatics software pipeline that achieves a much improved call rate …

Protein Modification By Arginylation, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

The modification of protein by arginine catalyzed by arginyltransferases (ATE1) described by the Kashina group in this issue shows that arginylation of protein occurs widely in biology and is being recognized as a key regulatory reaction such as phosphorylation of proteins (Wang et al., 2011).