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University of Massachusetts Amherst
Biochemistry & Molecular Biology Department Faculty Publication Series
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Full-Text Articles in Life Sciences
How The Protein Data Bank Changed Biology: An Introduction To The Jbc Reviews Thematic Series, Part 1, Helen M. Berman, Lila M. Gierasch
How The Protein Data Bank Changed Biology: An Introduction To The Jbc Reviews Thematic Series, Part 1, Helen M. Berman, Lila M. Gierasch
Biochemistry & Molecular Biology Department Faculty Publication Series
This collection of articles celebrates the 50th anniversary of the Protein Data Bank (PDB), the single global digital archive of biological macromolecular structures. The impact of the PDB is immense; we have invited a number of top researchers in structural biology to illustrate its influence on an array of scientific fields. What emerges is a compelling picture of the synergism between the PDB and the explosive progress witnessed in many scientific areas. Availability of reliable, openly accessible, well-archived structural information has arguably had more impact on cell and molecular biology than even some of the enabling technologies such as PCR. …
The Feronia Receptor Kinase Maintains Cell-Wall Integrity During Salt Stress Through Ca2+ Signaling, Wei Feng, Daniel Kita, Alexis Peaucelle, Heather N. Cartwright, Vinh Doan, Qiaohong Duan, Ming-Che Liu, Jacob Maman, Leonie Steinhorst, Ina Schmitz-Thom, Robert Yvon, Jörg Kudla, Hen-Ming Wu, Alice Y. Cheung, José R. Dinneny
The Feronia Receptor Kinase Maintains Cell-Wall Integrity During Salt Stress Through Ca2+ Signaling, Wei Feng, Daniel Kita, Alexis Peaucelle, Heather N. Cartwright, Vinh Doan, Qiaohong Duan, Ming-Che Liu, Jacob Maman, Leonie Steinhorst, Ina Schmitz-Thom, Robert Yvon, Jörg Kudla, Hen-Ming Wu, Alice Y. Cheung, José R. Dinneny
Biochemistry & Molecular Biology Department Faculty Publication Series
Cells maintain integrity despite changes in their mechanical properties elicited during growth and environmental stress. How cells sense their physical state and compensate for cell-wall damage is poorly understood, particularly in plants. Here we report that FERONIA (FER), a plasma-membrane-localized receptor kinase from Arabidopsis, is necessary for the recovery of root growth after exposure to high salinity, a widespread soil stress. The extracellular domain of FER displays tandem regions of homology with malectin, an animal protein known to bind di-glucose in vitro and important for protein quality control in the endoplasmic reticulum. The presence of malectin-like domains in FER …
Mechanistic Insights Into The Cholesterol-Dependent Binding Of Perfringolysin O-Based Probes And Cell Membranes, Alejandro Heuck, Juan Anguita, Benjamin B. Johnson, Mariana Brena
Mechanistic Insights Into The Cholesterol-Dependent Binding Of Perfringolysin O-Based Probes And Cell Membranes, Alejandro Heuck, Juan Anguita, Benjamin B. Johnson, Mariana Brena
Biochemistry & Molecular Biology Department Faculty Publication Series
Cholesterol distribution in the cell is maintained by both vesicular and non-vesicular sterol transport. Non-vesicular transport is mediated by the interaction of membrane-embedded cholesterol and water-soluble proteins. Small changes to the lipid composition of the membrane that do not change the total cholesterol content, can significantly affect how cholesterol interacts with other molecules at the surface of the membrane. The cholesterol-dependent cytolysin Perfringolysin O (PFO) constitutes a powerful tool to detect cholesterol in membranes, and the use of PFO-based probes has flourished in recent years. By using a non-lytic PFO derivative, we showed that the sensitivity of the probes for …
Molecular Mechanism Of Activation-Triggered Subunit Exchange In Human Camkii, M Bhattacharyya, Margaret M. Stratton, Catherine Going, Yongjian Huang, Ethan Mcspadden, Anna Elleman, Pawel Burkhwat, Tiago Barros, Evan Williams, John Kuriyan
Molecular Mechanism Of Activation-Triggered Subunit Exchange In Human Camkii, M Bhattacharyya, Margaret M. Stratton, Catherine Going, Yongjian Huang, Ethan Mcspadden, Anna Elleman, Pawel Burkhwat, Tiago Barros, Evan Williams, John Kuriyan
Biochemistry & Molecular Biology Department Faculty Publication Series
Activation triggers the exchange of subunits in Ca2+/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the …
Human Acid Sphingomyelinase Structures Provide Insight To Molecular Basis Of Niemann-Pick Disease, Yan-Feng Zhou, Matthew C. Metcalf, Scott C. Garman, Tim Edmunds, Huawei Qiu, Ronnie R. Wei
Human Acid Sphingomyelinase Structures Provide Insight To Molecular Basis Of Niemann-Pick Disease, Yan-Feng Zhou, Matthew C. Metcalf, Scott C. Garman, Tim Edmunds, Huawei Qiu, Ronnie R. Wei
Biochemistry & Molecular Biology Department Faculty Publication Series
Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal …
Activation-Triggered Subunit Exchange Between Camkii Holoenzymes Facilitates The Spread Of Kinase Activity, Margaret M. Stratton, I H. Lee, M Bhattacharyya, S M. Christensen, L H. Chao, H Schulman, J T. Groves, J Kuriyan
Activation-Triggered Subunit Exchange Between Camkii Holoenzymes Facilitates The Spread Of Kinase Activity, Margaret M. Stratton, I H. Lee, M Bhattacharyya, S M. Christensen, L H. Chao, H Schulman, J T. Groves, J Kuriyan
Biochemistry & Molecular Biology Department Faculty Publication Series
The activation of the dodecameric Ca2+/calmodulin dependent kinase II (CaMKII) holoenzyme is critical for memory formation. We now report that CaMKII has a remarkable property, which is that activation of the holoenzyme triggers the exchange of subunits between holoenzymes, including unactivated ones, enabling the calcium-independent phosphorylation of new subunits. We show, using a single-molecule TIRF microscopy technique, that the exchange process is triggered by the activation of CaMKII, and that exchange is modulated by phosphorylation of two residues in the calmodulin-binding segment, Thr 305 and Thr 306. Based on these results, and on the analysis of molecular dynamics simulations, we …
Converting A Protein Into A Switch For Biosensing And Functional Regulation, Margaret M. Stratton, S N. Loh
Converting A Protein Into A Switch For Biosensing And Functional Regulation, Margaret M. Stratton, S N. Loh
Biochemistry & Molecular Biology Department Faculty Publication Series
Proteins that switch conformations in response to a signaling event (e.g., ligand binding or chemical modification) present a unique solution to the design of reagent-free biosensors as well as molecules whose biological functions are regulated in useful ways. The principal roadblock in the path to develop such molecules is that the majority of natural proteins do not change conformation upon binding their cognate ligands or becoming chemically modified. Herein, we review recent protein engineering efforts to introduce switching properties into binding proteins. By co-opting natural allosteric coupling, joining proteins in creative ways and formulating altogether new switching mechanisms, researchers are …
Multiple Domains In The Crumbs Homolog 2a (Crb2a) Protein Are Required For Regulating Rod Photoreceptor Size, Abigail Jensen, Ya-Chu Hsu
Multiple Domains In The Crumbs Homolog 2a (Crb2a) Protein Are Required For Regulating Rod Photoreceptor Size, Abigail Jensen, Ya-Chu Hsu
Biochemistry & Molecular Biology Department Faculty Publication Series
Background Vertebrate retinal photoreceptors are morphologically complex cells that have two apical regions, the inner segment and the outer segment. The outer segment is a modified cilium and is continuously regenerated throughout life. The molecular and cellular mechanisms that underlie vertebrate photoreceptor morphogenesis and the maintenance of the outer segment are largely unknown. The Crumbs (Crb) complex is a key regulator of apical membrane identity and size in epithelia and in Drosophila photoreceptors. Mutations in the human gene CRUMBS HOMOLOG 1 (CRB1) are associated with early and severe vision loss. Drosophila Crumbs and vertebrate Crb1 and Crumbs homolog 2 (Crb2) …
Probing Local Structural Fluctuations In Myoglobin By Size-Dependent Thiol-Disulfide Exchange, Margaret M. Stratton, S N. Loh, T A. Cutler, J H. Ha
Probing Local Structural Fluctuations In Myoglobin By Size-Dependent Thiol-Disulfide Exchange, Margaret M. Stratton, S N. Loh, T A. Cutler, J H. Ha
Biochemistry & Molecular Biology Department Faculty Publication Series
All proteins undergo local structural fluctuations (LSFs) or breathing motions. These motions are likely to be important for function but are poorly understood. LSFs were initially defined by amide hydrogen exchange (HX) experiments as opening events, which expose a small number of backbone amides to (1)H/(2)H exchange, but whose exchange rates are independent of denaturant concentration. Here, we use size-dependent thiol-disulfide exchange (SX) to characterize LSFs in single cysteine-containing variants of myoglobin (Mb). SX complements HX by providing information on motions that disrupt side chain packing interactions. Most importantly, probe reagents of different sizes and chemical properties can be used …
On The Mechanism Of Protein Fold-Switching By A Molecular Sensor, Margaret M. Stratton, S N. Loh
On The Mechanism Of Protein Fold-Switching By A Molecular Sensor, Margaret M. Stratton, S N. Loh
Biochemistry & Molecular Biology Department Faculty Publication Series
Alternate frame folding (AFF) is a mechanism by which conformational change can be engineered into a protein. The protein structure switches from the wild-type fold (N) to a circularly-permuted fold (N'), or vice versa, in response to a signaling event such as ligand binding. Despite the fact that the two native states have similar structures, their interconversion involves folding and unfolding of large parts of the molecule. This rearrangement is reported by fluorescent groups whose relative proximities change as a result of the order-disorder transition. The nature of the conformational change is expected to be similar from protein to protein; …
Tissue-Specific Requirements For Specific Domains In The Ferm Protein Moe/Epb4.1l5 During Early Zebrafish Development, Arne K. Christensen, Abigail Jensen
Tissue-Specific Requirements For Specific Domains In The Ferm Protein Moe/Epb4.1l5 During Early Zebrafish Development, Arne K. Christensen, Abigail Jensen
Biochemistry & Molecular Biology Department Faculty Publication Series
Background The FERM domain containing protein Mosaic Eyes (Moe) interacts with Crumbs proteins, which are important regulators of apical identity and size. In zebrafish, loss-of-function mutations in moe result in defects in brain ventricle formation, retinal pigmented epithelium and neural retinal development, pericardial edema, and tail curvature. In humans and mice, there are two major alternately spliced isoforms of the Moe orthologue, Erythrocyte Protein Band 4.1-Like 5 (Epb4.1l5), which we have named Epb4.1l5long and Epb4.1l5short, that differ after the FERM domain. Interestingly, Moe and both Epb4.1l5 isoforms have a putative C' terminal Type-I PDZ-Binding Domain (PBD). We previously showed that …