Description

Project Summary The Membrane Proteins in Infectious Diseases (MPID) Center (5U54GM094599-04) at Arizona State University focuses on determining structures for membrane proteins of important viral and bacterial pathogens, as well as human membrane proteins that are involved in pathogenic pathways during infection. Membrane proteins represent>60% of all drug targets and they are also key players in the pathogenesis of infectious agents. Understanding the structure, dynamics and function of membrane proteins during infection is critical for development of anti-microbial therapeutic approaches and vaccine platforms against infectious agents. Our knowledge of processes catalyzed by membrane proteins suffers because of the lack of information concerning their structure. The Centers theme is unique and the results and structures that are being determined are highly relevant for human health worldwide because structural information can provide important clues for the understanding infectious disease pathways and thus, form the basis for treatment and prevention. The major goal of the Center is to determine the structures of more than 40 novel membrane protein structures and to develop new technology for high throughput membrane protein expression, isolation, functional characterization, crystallization, and structure determination. The Center aims to significantly contribute to the main goal of the PSI structure initiative by solving structures of novel membrane proteins with a large sequence and structural coverage. The Center also aims to develop new bioinformatics tools for the analysis of potential targets, solved structures, and the prediction of membrane protein structures. The current proposal requests a supplement to support a trainee whose success will help promote diversity in healthrelated research. The trainee plans to pursue a MD-Ph.D. and has an overall goal is to pursue a career that combines fundamental research and patient care to improve healthcare outcomes. The overall goal of the proposed research plan is to increase the trainees research experience and provide career guidance/mentoring to help strengthen his competiveness for entry into a highly competitive medical-graduate program and success as he moves forward. The research plan for the trainee focuses on coronavirus envelope (E) proteins and their structure and functional roles in virus assembly, egress from cells and virulence during infection. E proteins are viroporins that exhibit ion channel activity in vitro, but their functional role in during infection at intracellular membranes is not fully understood. The research aims are to (1) identify critical amino acids in the transmembrane domain of coronavirus envelope (E) proteins that are functionally important for ion channel activity and (2) determine how alteration of residues that affect ion channel activity impact the structure of the protein.

Description

The MPID Center for membrane protein structure determination is focused on an important biological and medically relevant theme. It aims to determine the structures of membrane proteins involved in pathogenesis, with a focus on viral membrane proteins, bacterial membrane proteins, and human membrane proteins involved in pathogenic pathways. Membrane proteins represent >60% of all drug targets and they are also key players in the pathogenesis of infectious diseases. A critical step for the elucidation of the complex processes that are catalyzed by membrane proteins is an understanding of the structure, dynamics and function of membrane proteins. Our knowledge of processes catalyzed by membrane proteins suffers mainly from the lack of information concerning their structure as less than 300 different membrane protein structures are known at present. The Center targets membrane proteins of important viral and bacterial pathogens, their infectious pathways, and molecules involved in host defense against the pathogens. This theme is unique and the results and structures determined by the Center will be highly relevant for human health worldwide. The structure determination of each of the targets may provide important clues for the understanding of the infectious disease pathways and can therefore form the basis for the treatment and prevention of infectious diseases. The major goal of the Center is to use the biological theme of membrane proteins in infectious diseases as the basis for the determination of more than 40 novel membrane protein structures and to develop new technology for high throughput membrane protein expression, isolation, functional characterization, crystallization, and structure determination. Therefore, the Center aims to significantly contribute to the main goal of the PSI structure initiative by solving structures of novel membrane proteins with a large sequence and structural coverage. The Center also aims to develop new bioinformatics tools for the analysis of potential targets, solved structures, and the prediction of membrane protein structures. The MPID center will also collaborate with the community and the PSI on the structure determination of target membrane proteins that complement the initial targets of the center.
StatusFinished
Effective start/end date7/1/116/30/16

Funding

  • HHS-NIH: National Institute of General Medical Sciences (NIGMS): $5,689,118.00

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Communicable Diseases
Membrane Proteins
Viral Matrix Proteins
Ion Channels
Research
Coronavirus
Crystallization
Infection
Computational Biology
Competitive Bidding
Proteins
Technology
Virus Release
Virus Assembly
Intracellular Membranes
Bacterial Proteins