Biochemistry, Biophysics, and Structural Biology Commons^™

Regulation Of Phialide Morphogenesis In Aspergillus Nidulans, Hu Yin

School of Biological Sciences: Dissertations, Theses, and Student Research

Filamentous fungi have two distinctive life cycles, vegetative growth and development for sexual or asexual spore formation. The asexual reproduction in development as conidiation in A. nidulans is the dominant form of producing spores effectively. A complex conidiophore structure is developed during asexual reproduction process. The conidiophore is formed from hyphal cell and consists of stalk, vesicle, metulae, phialide and conidial spores. Phialides are essential sporogenous cells in the conidiophore structure. The growth pattern is switched from acropetal to basipetal between phialide and spores, which makes phialide a unique cell type in A. nidulans and other phialide producing fungi. Study …

Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses.

METHODS. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme …

Design, Assessment, And In Vivo Evaluation Of A Computational Model Illustrating The Role Of Cav1 In Cd4+ T-Lymphocytes, Brittany D. Conroy, Tyler A. Herek, Timonthy D. Shew, Matthew Latner, Joshua J. Larson, Laura Allen, Paul H. Davis, Tomáš Helikar, Christine E. Cutucache

Department of Biochemistry: Faculty Publications

Caveolin-1 (CAV1) is a vital scaffold protein heterogeneously expressed in both healthy and malignant tissue. We focus on the role of CAV1 when overexpressed in T-cell leukemia. Previously, we have shown that CAV1 is involved in cell-to-cell communication, cellular proliferation, and immune synapse formation; however, the molecular mechanisms have not been elucidated.We hypothesize that the role of CAV1 in immune synapse formation contributes to immune regulation during leukemic progression, thereby warranting studies of the role of CAV1 in CD4⁺ T-cells in relation to antigen-presenting cells. To address this need, we developed a computational model of a CD4⁺ immune …

Glutaredoxin 2 (Grx2) Gene Deletion Induces Early Onset Of Age-Dependent Cataracts In Mice, Hongli Wu, Yibo Yu, Larry David, Ye-Shih Ho, Marjorie . F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and it controls thiol/ disulfide balance in cells. In this study, we investigated whether Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knock-out (KO) mice and age-matched wild-type (WT) mice ages 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than …

The Development Of A Valid And Reliable Biogeochemistry Concept Inventory, Chris Mead

DBER Speaker Series

Concept inventories are a commonly used tool to measure conceptual understanding. To date, concept inventories have been published for geology, chemistry, and biology, but no instrument has been designed to measure conceptual understanding at the intersection of those fields. To fill that gap, we constructed a 32‐item biogeochemistry concept inventory (BGC‐CI). Item response theory analysis, using the Rasch model, shows the BGC‐CI is a reliable and valid tool to measure the biogeochemistry knowledge of science majors. Because biogeochemistry is an interdisciplinary field, we were concerned about the unidimensionality of the instrument. However, our analysis showed the BGC‐CI to be acceptably …

Er-Associated Degradation And Cadmium Dependent Rescue Of Pca1, Nathan Smith

Department of Biochemistry: Dissertations, Theses, and Student Research

Protein synthesis and proper folding is an essential process for all organisms. In eukaryotes proteins of the secretory pathway are synthesized and inserted into the lumen or membrane of the endoplasmic reticulum. Eukaryotic cells maintain a mechanism for removal of proteins unable to fold properly. This process is known as ER-associated degradation (ERAD). A poorly functioning ERAD can lead to a build-up of misfolded proteins which has been implicated in several degenerative diseases such as Alzheimer’s, Amyotrophic lateral sclerosis, and Parkinson’s. Thus, the study of how proteins are recognized, extracted from the ER, and degraded is essential for determining methods …

Overexpression Of Patatin-Related Phospholipase Aiiiβ Altered The Content And Composition Of Sphingolipids In Arabidopsis, Maoyin Li, Jennifer E. Markham, Xuemin Wang

Department of Biochemistry: Faculty Publications

In plants, fatty acids are primarily synthesized in plastids and then transported to the endoplasmic reticulum (ER) for synthesis of most of the complex membrane lipids, including glycerolipids and sphingolipids. The first step of sphingolipid synthesis, which uses a fatty acid and a serine as substrates, is critical for sphingolipid homeostasis; its disruption leads to an altered plant growth. Phospholipase As have been implicated in the trafficking of fatty acids from plastids to the ER. Previously, we found that overexpression of a patatin-related phospholipase, pPLAIIIβ, resulted in a smaller plant size and altered anisotropic cell expansion. Here, we determined the …

A Rational Framework For Evaluating The Next Generation Of Vaccines Against Mycobacterium Avium Subspecies Paratuberculosis, John P. Bannantine, Murray E. Hines Ii, Luiz E. Bermudez, Adel M. Talaat, Srinand Sreevatsan, Judith R. Stabel, Yung-Fu Chang, Paul M. Coussens, Raúl G. Barletta, William C. Davis, Desmond M. Collins, Yrjö T. Gröhn, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Since the early 1980s, several investigations have focused on developing a vaccine against Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease in cattle and sheep. These studies used whole-cell inactived vaccines that have proven useful in limiting disease progression, but have not prevented infection. In contrast, modified live vaccines that invoke a Th1 type immune response, may improve protection against infection. Spurred by recent advances in the ability to create defined knockouts in MAP, several independent laboratories have developed modified live vaccine candidates by transcriptional mutation of virulence and metablolic genes in MAP. In order to accelerate …

Sensitivity Analysis Of Biological Boolean Networks Using Information Fusion Based On Nonadditive Set Functions, Naomi Kochi, Tomáš Helikar, Laura Allen, Jim A. Rogers, Zhenyuan Wang, Mihaela T. Matache

Department of Biochemistry: Faculty Publications

Background: An algebraic method for information fusion based on nonadditive set functions is used to assess the joint contribution of Boolean network attributes to the sensitivity of the network to individual node mutations. The node attributes or characteristics under consideration are: in-degree, out-degree, minimum and average path lengths, bias, average sensitivity of Boolean functions, and canalizing degrees. The impact of node mutations is assessed using as target measure the average Hamming distance between a non-mutated/wild-type network and a mutated network.

Results: We find that for a biochemical signal transduction network consisting of several main signaling pathways whose nodes …

Use Of Cysteine-Reactive Crosslinkers To Probe Conformational Flexibility Of Human Dj-1 Demonstrates That Glu18 Mutations Are Dimers, Janani Prahlad, David N. Hauser, Nicole M. Milkovic, Mark R. Cookson, Mark A. Wilson

Department of Biochemistry: Faculty Publications

The oxidation of a key cysteine residue (Cys106) in the parkinsonism-associated protein DJ-1 regulates its ability to protect against oxidative stress and mitochondrial damage. Cys106 interacts with a neighboring protonated Glu18 residue, stabilizing the Cys106-SO₂ ⁻ (sulfinic acid) form of DJ-1. To study this important post-translational modification, we previously designed several Glu18 mutations (E18N, E18D, E18Q) that alter the oxidative propensity of Cys106. However, recent results suggest these Glu18 mutations cause loss of DJ-1 dimerization, which would severely compromise the protein’s function. The purpose of this study was to conclusively determine the oligomerization state of these mutants using X-ray …

Single Tube, Multiple Enzyme Reaction For Detection Of Uv And Oxidative Damage In Forensic Physiological Stains, Nicholas J. Eurek

Department of Biochemistry: Dissertations, Theses, and Student Research

For decades, the use of DNA as a biological tool has revolutionized forensic investigations. The primary use of this genetic evidence is for identification of a victim or suspect through short tandem repeat (STR) profiling. However, the usefulness of this evidence can be compromised through inhibition of PCR, damage to the DNA, or low copy number. Here, we investigate damage induced to DNA by environmental factors. UV light is known to damage DNA by the formation of cyclobutane pyrimidine dimers, 6-4 photoproducts, and strand breaks. These lesions can stall polymerase action or misincorporate bases during extension. Oxidative damage is also …

Gmos: Are They A Regulatory Or Food Safety Issue?, Richard E. Goodman

Department of Food Science and Technology: Faculty Publications

Most of the genetic diversity that has improved agricultural production throughout the history of farming was developed through natural mutations and selective breeding. However, since the early 1900s plant scientists have used chemical and radiation mutagenesis to increase genetic diversity (18). We know that the majority of mutations are harmful, and plant breeders work hard to select only those that are beneficial. This process has helped feed a growing human population, which is estimated to have been 300 million 2,000 years ago and is now more than 7 billion. However, methods used in the past to improve agricultural production are …

Evaluation Of Eight Live Attenuated Vaccine Candidates For Protection Against Challenge With Virulent Mycobacterium Avium Subspecies Paratuberclosis In Mice, John Bannantine, Jamie L. Everman, Sasha J. J.Rose, Lmar Babrak, Robab Katani, Raul G. Barletta, Adel M. Talaat, Yrjö J. Gröhn, Yung-Fu Chang, Vivek Kapur, Luiz E. Bermudez

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne's disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistaence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants …

The Evolution Of Respiratory O2/No Reductases: An Out-Of-The-Phylogenetic-Box Perspective, Anne-Lise Ducluzeau, Barbara Schoepp-Cothenet, Robert Van Lis, Frauke Baymann, Michael J. Russell, Wilfgang Nitschke

Department of Biochemistry: Faculty Publications

Complex life on our planet crucially depends on strong redox disequilibria afforded by the almost ubiquitous presence of highly oxidizing molecular oxygen. However, the history of O₂-levels in the atmosphere is complex and prior to the Great Oxidation Event some 2.3 billion years ago, the amount of O₂ in the biosphere is considered to have been extremely low as compared with present-day values. Therefore the evolutionary histories of life and of O₂-levels are likely intricately intertwined. The obvious biological proxy for inferring the impact of changing O₂-levels on life is the evolutionary history …

The Mechanism Of Small Rna Biogenesis, Degradation, And Function In Arabidopsis, Meng Xie

School of Biological Sciences: Dissertations, Theses, and Student Research

Eukaryotic small RNAs play important roles in many biological processes through sequence-specific RNA silencing. In plants, there are mainly two small RNAs triggering gene silencing: microRNAs (miRNAs) and small interfering RNAs (siRNAs). The biogenesis and precise regulation of small RNA abundance are crucial for plant growth, development, genomic stability, and the resistance to both abiotic and biotic stresses. In this study, we used Arabidopsis thaliana, the model plant, to study the mechanism of RNA-directed DNA methylation (RdDM), in which siRNAs can trigger DNA methylation and gene silencing. In addition, we investigated the mechanism of miRNA biogenesis and degradation. For …

Conformationally Stabilized Hiv Envelope Immunogens, Peter Kwong, John Mascola, Gary Nabel, Richard Wyatt, Barna Dey, Ling Xu, Tongqing Zhou, Joseph Sodroski, Wen Yuan, Shi-Hua Xiang

School of Veterinary and Biomedical Sciences: Faculty Publications

Isolated immunogens including a HIV-1 gp120 polypeptide or immunogenic fragment thereof stabilized in a CD4 bound confirmation by crosslinked cysteines, and methods of their use are disclosed. The immunogens are useful, for example, for generating an immune response to HIV-1 gp120 in a Subject.

Stress Responses And Energy Storage In Drosophila Melanogaster Selected For Resistance To A Gram-Positive Bacillus Cereus Spores, Zhen Hu

School of Biological Sciences: Dissertations, Theses, and Student Research

A survival response study was carried out by using D. melanogaster and the opportunistic pathogen B. cereus as the agent of selection. The spores of B. cereus, a gram-positive bacteria that can cause the human pathogen disease, were applied in our artificial laboratory selection. Selected lines were treated with B. cereus spores. Wound control lines were punctured with a needle dipped into sterile H₂O. Control lines did not apply any treatment. Three different environmental treatments were used within each line type (autoclaved spores of B.cereus, sterile H₂O and no treatment). The autoclaved spores were …

Methionine Restriction Extends Lifespan Of Drosophila Melanogaster Under Conditions Of Low Amino-Acid Status, Byung Cheon Lee, Alaattin Kaya, Siming Ma, Gwansu Kim, Maxim V. Gerashchenko, Sun Hee Yim, Zhen Hu, Lawrence G. Harshman, Vadim N. Gladyshev

Lawrence G. Harshman Publications

Reduced methionine (Met) intake can extend lifespan of rodents; however, whether this regimen represents a general strategy for regulating aging has been controversial. Here we report that Met restriction extends lifespan in both fruit flies and yeast, and that this effect requires low amino-acid status. Met restriction in Drosophila mimicks the effect of dietary restriction and is associated with decreased reproduction. However, under conditions of high amino-acid status, Met restriction is ineffective and the trade-off between longevity and reproduction is not observed. Overexpression of InRDN or Tsc2 inhibits lifespan extension by Met restriction, suggesting the role of TOR signalling in …

Cd8Α Dendritic Cells Drive Establishment Of Hsv-1 Latency, Kevin R. Mott, Sariah J. Allen, Mandana Zandian, Bindu Konda, Behrooz G. Sharifi, Clinton Jones, Steven L. Wechsler, Terrence Town, Homayon Ghiasi

School of Veterinary and Biomedical Sciences: Faculty Publications

It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little is known about the role of innate immunity in establishment of viral latency. In the current study, we investigated whether CD8α DCs impact HSV-1 latency by examining latency in the trigeminal ganglia (TG) of wildtype (WT) C57BL/6 versus CD8α^‒/‒ (lack functional CD8 T cells and CD8α⁺ DCs), CD8β^‒/‒ (have functional CD8α⁺ T cells and CD8α⁺ DCs), and β2m^‒/‒ (lack functional CD8 T cells but have CD8α^{+ …}

A Course-Based Research Experience: How Benefits Change With Increased Investment In Instructional Time, Christopher D. Shaffer, Cheryl Bailey, Students And Tas In Genomics Education Partnership Courses

Department of Biochemistry: Faculty Publications

There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge.We have developed a bioinformatics project that provides a coursebased research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant investment …

Redox Regulation Of Protein Translation In Eukaryotes, Maxim Gerashchenko

Department of Biochemistry: Dissertations, Theses, and Student Research

Gene expression may be controlled at multiple levels, e.g., through genomic architecture, transcription and translation. In the current work, we focused on regulation of protein synthesis. Historically, the investigation of the regulation of gene expression at the level of translation lagged behind the transcriptional control because of the lack of accessible high-throughput methods. Our research has begun with the finding of the use of alternative non-AUG start codon in thioredoxin-glutathione reductase (TGR), a selenoprotein involved in redox control during male reproduction. The use of this codon, CUG, relies on the Kozak consensus sequence and ribosomal scanning mechanism. However, the CUG …

The Role Of Sirtuin 1 And Ceramide In T10C12 Conjugated Linoleic Acid Induced Delipidation In 3t3-L1 Adipocytes, Wei Wang

Department of Animal Science: Dissertations, Theses, and Student Research

Project 1: Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride (TG) levels in adipocytes through multiple pathways, with AMP-activated protein kinase (AMPK) generally facilitating, and peroxisome proliferator-activated receptor γ (PPARγ) generally opposing these reductions. Sirtuin 1 (SIRT1), a histone/protein deacetylase that affects energy homeostasis, often functions coordinately with AMPK, and is capable of binding to PPARγ, thereby inhibiting its activity. This study investigated the role of SIRT1 in the response of 3T3-L1 adipocytes to t10c12 CLA by testing the following hypotheses: 1) SIRT1 is functionally required for robust TG reduction; …

Overexpression Of Thioredoxin Binding Protein (Tbp-2) Increases Oxidation Sensitivity And Apoptosis In Human Lens Epithelial Cells, Yibo Yu, Kuiyi Xing, Rilwan Badamas, Charles A. Kuszynski, Hongli Wuand, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Thioredoxin (Trx) is an important redox regulator with cytosolic Trx1 and mitochondrial Trx2 isozymes. Trx has multi-physiological functions in cells and its bioavailability is negatively controlled through active site binding to a specific thioredoxin binding protein (TBP-2). This paper describes the delicate balance between TBP-2 and Trx, and the effect of overexpression of TBP-2 in the human lens epithelial cells. Cells overexpressing TBP-2 (TBP-2 OE) showed a 7- fold increase of TBP-2, and a nearly 40% suppression of Trx activity but no change in Trx expression. The TBP-2 OE cells grew slower and their population decreased to 30% by day …

Systems Thinking With Biology Models, Joseph Dauer

DBER Speaker Series

The recent AAAS call to improve undergraduate biology education suggested university instruction should focus on teaching core concepts like matter and energy, evolution, and systems and core competences like quantitative reasoning, modeling and integrating disciplines. My research has focused on how undergraduate biology students organize their knowledge of biological systems and how they reason about the myriad interactions and potential outcomes inherent to these systems. I will report ongoing research into students’ model construction during an introductory biology course and during clinical interviews 2 years after the course. My colleagues and I have found students’ models change dramatically in both …

Evaluation Of Novel Oral Vaccine Candidates And Validation Of A Caprine Model Of Johne’S Disease, Murray E. Hines Ii, Sue E. Turnquist, Marcia R.S. Ilha, Sreekumari Rajeev, Arthur L. Jones, Lisa Whittington, John P. Bannantine, Raul G. Barletta, Yrjö T. Gröhn, Robab Katani, Adel M. Talaat, Lingling Li, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne’s disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn’s disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne’s Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne’s disease go at challenge model. …

Structures Of The Puta Peripheral Membrane Flavoenzyme Reveal A Dynamic Substrate-Channeling Tunnel And The Quinone-Binding Site, Harkewal Singh, Benjamin W. Arentson, Donald F. Becker, John J. Tanner

Department of Biochemistry: Faculty Publications

Proline utilization A (PutA) proteins are bifunctional peripheral membrane flavoenzymes that catalyze the oxidation of L-proline to L-glutamate by the sequential activities of proline dehydrogenase and aldehyde dehydrogenase domains. Located at the inner membrane of Gram-negative bacteria, PutAs play a major role in energy metabolism by coupling the oxidation of proline imported from the environment to the reduction of membrane-associated quinones. Here, we report seven crystal structures of the 1,004- residue PutA from Geobacter sulfurreducens, along with determination of the protein oligomeric state by small-angle X-ray scattering and kinetic characterization of substrate channeling and quinone reduction. The structures reveal …

Genome-Wide Rnai Ionomics Screen Reveals New Genes And Regulation Of Human Trace Element Metabolism, Mikalai I. Malinouski, Nesrin M. Hasan, Yan Zhang, Javier Seravalli, Jie Lin, Andrei Avanesov, Svetlana Lutsenko, Vadim N. Gladyshev

Department of Biochemistry: Faculty Publications

Trace elements are essential for human metabolism and dysregulation of their homoeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundamental differences in the regulation of different trace elements. Specifically, selenium levels are controlled through the selenocysteine machinery and expression of abundant selenoproteins; copper balance is affected by lipid metabolism and requires …

Metabolic Reprogramming Induced By Ketone Bodies Diminishes Pancreatic Cancer Cachexia, Surendra K. Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V. Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I. Pipinos, Robert Powers, Fang Yu, Pankaj K. Singh

Robert Powers Publications

Background: Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in …

Effects Of 5-Hydroxytryptamine 2c Receptor Agonist Mk212 And 2a Receptor Antagonist Mdl100907 On Maternal Behavior In Postpartum Female Rats, Weihai Chen, Qi Zhang, Wenxin Su, Yu Yang, Jing Qiao, Nan Sui, Ming Li

Department of Psychology: Faculty Publications

Maternal behavior in rats is a highly motivated and well-organized social behavior. Given the known roles of serotonin (5-HT) in emotion, motivation, social behavior, and major depression – and its known interaction with dopamine – it is likely that serotonin also plays a crucial role in this behavior. So far, there are surprisingly few studies focusing on 5-HT in maternal behavior, except for maternal aggression. In the present study,we examined the effects of 5-HT_2C receptor agonism and 5-HT_2A receptor antagonism on maternal behavior in postpartum female rats.We hypothesized that activation of 5-HT_2C receptors and blockade of 5-HT …

Arabidopsis Accelerated Cell Death 11, Acd11, Is A Ceramide-1-Phosphate Transfer Protein And Intermediary Regulator Of Phytoceramide Levels, Dhirendra K. Simanshu, Xiuhong Zhai, David Munch, Daniel Hofius, Jennifer E. Markham, Jacek Bielawski, Alicja Bielawska, Lucy Malinina, Julian G. Molotkovsky, John W. Mundy, Dinshaw J. Patel, Rhoderick E. Brown

Department of Biochemistry: Faculty Publications

The accelerated cell death 11 (acd11) mutant of Arabidopsis provides a genetic model for studying immune response activation and localized cellular suicide that halt pathogen spread during infection in plants. Here, we elucidate ACD11 structure and function and show that acd11 disruption dramatically alters the in vivo balance of sphingolipid mediators that regulate eukaryotic-programmed cell death. In acd11 mutants, normally low ceramide-1- phosphate (C1P) levels become elevated, but the relatively abundant cell death inducer phytoceramide rises acutely. ACD11 exhibits selective intermembrane transfer of C1P and phyto-C1P. Crystal structures establish C1P binding via a surface-localized, phosphate headgroup recognition center …