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.

Public Health Relevance

The major goal of the Center for Membrane Proteins in Infectious Diseases is to determine structures of membrane proteins involved in pathogenesis. The focus is on medically important viral and bacterial membrane proteins and human membrane proteins involved in their pathogenic pathways. The Center uses the biological theme of infectious diseases as the basis for the determination of novel membrane protein structures and to develop new technologies for high throughput membrane protein expression, isolation, functional characterization, crystallization and structure determination.

Agency
National Institute of Health (NIH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM094599-05
Application #
8692904
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Type
DUNS #
City
Tempe
State
AZ
Country
United States
Zip Code
85287
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Boland, CoilĂ­n; Li, Dianfan; Shah, Syed Tasadaque Ali et al. (2014) Cell-free expression and in meso crystallisation of an integral membrane kinase for structure determination. Cell Mol Life Sci 71:4895-910
Li, Dianfan; Caffrey, Martin (2014) Renaturing membrane proteins in the lipid cubic phase, a nanoporous membrane mimetic. Sci Rep 4:5806
Nji, Emmanuel; Li, Dianfan; Doyle, Declan A et al. (2014) Cloning, expression, purification, crystallization and preliminary X-ray diffraction of a lysine-specific permease from Pseudomonas aeruginosa. Acta Crystallogr F Struct Biol Commun 70:1362-7
Domingo Meza-Aguilar, J; Fromme, Petra; Torres-Larios, Alfredo et al. (2014) X-ray crystal structure of the passenger domain of plasmid encoded toxin(Pet), an autotransporter enterotoxin from enteroaggregative Escherichia coli (EAEC). Biochem Biophys Res Commun 445:439-44
Caffrey, Martin; Li, Dianfan; Howe, Nicole et al. (2014) 'Hit and run' serial femtosecond crystallography of a membrane kinase in the lipid cubic phase. Philos Trans R Soc Lond B Biol Sci 369:20130621
Tan, Jingquan; Rouse, Sarah L; Li, Dianfan et al. (2014) A conformational landscape for alginate secretion across the outer membrane of Pseudomonas aeruginosa. Acta Crystallogr D Biol Crystallogr 70:2054-68
Li, Dianfan; Howe, Nicole; Dukkipati, Abhiram et al. (2014) Crystallizing Membrane Proteins in the Lipidic Mesophase. Experience with Human Prostaglandin E2 Synthase 1 and an Evolving Strategy. Cryst Growth Des 14:2034-2047

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