Proteins are functional molecules in living systems and carry out most beneficial and deleterious function that affects life. A single protein may be involved in many different functional pathways and in living cells, interactions among proteins are the single strongest determinants that drive function. Therefore, the greatest opportunity to map coordinates of protein function for unknown or uncharacterized gene products would be presented if protein interaction networks that involve these proteins could visualized. The Protein Interaction Technology Core in this project is the product of many years of development efforts to pioneer new capabilities for visualization of protein interaction networks in live cells. This core will provide novel cross-linking and protein interaction identification technologies to support the overarching goal to place uncharacterized gene products within protein interaction networks in live A. baumannii cells. Through the core efforts to identify cross-linked peptides, interacting partner proteins and topological features of these interactions will be visualized. These data will form the basis of new interaction networks that can be mapped onto existing crystal structures for homologous or orthologous proteins and existing networks in other organisms to help link uncharacterized genes.

Public Health Relevance

Neariy all diseases are mediated by proteins and the ability to comprehend function of uncharacterized proteins requires increased efforts to identify protein-protein interactions that exist in cells. This Core will identify protein-protein interaction networks in the pathogen A. baumannii to help map functionality of uncharacterized genes in these bacteria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI107775-02
Application #
8688150
Study Section
Special Emphasis Panel (ZAI1-FDS-M)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$227,684
Indirect Cost
$94,712
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Karalewitz, Andrew P-A; Miller, Samuel I (2018) Multidrug-Resistant Acinetobacter baumannii Chloramphenicol Resistance Requires an Inner Membrane Permease. Antimicrob Agents Chemother 62:
Chavez, Juan D; Lee, Chi Fung; Caudal, Arianne et al. (2018) Chemical Crosslinking Mass Spectrometry Analysis of Protein Conformations and Supercomplexes in Heart Tissue. Cell Syst 6:136-141.e5
Vreven, Thom; Schweppe, Devin K; Chavez, Juan D et al. (2018) Integrating Cross-Linking Experiments with Ab Initio Protein-Protein Docking. J Mol Biol 430:1814-1828
Zhong, Xuefei; Navare, Arti T; Chavez, Juan D et al. (2017) Large-Scale and Targeted Quantitative Cross-Linking MS Using Isotope-Labeled Protein Interaction Reporter (PIR) Cross-Linkers. J Proteome Res 16:720-727
Gallagher, Larry A; Lee, Samuel A; Manoil, Colin (2017) Importance of Core Genome Functions for an Extreme Antibiotic Resistance Trait. MBio 8:
Schweppe, Devin K; Chavez, Juan D; Lee, Chi Fung et al. (2017) Mitochondrial protein interactome elucidated by chemical cross-linking mass spectrometry. Proc Natl Acad Sci U S A 114:1732-1737
Miller, Samuel I (2016) Antibiotic Resistance and Regulation of the Gram-Negative Bacterial Outer Membrane Barrier by Host Innate Immune Molecules. MBio 7:
Baric, Ralph S; Crosson, Sean; Damania, Blossom et al. (2016) Next-Generation High-Throughput Functional Annotation of Microbial Genomes. MBio 7:
Chavez, Juan D; Schweppe, Devin K; Eng, Jimmy K et al. (2016) In Vivo Conformational Dynamics of Hsp90 and Its Interactors. Cell Chem Biol 23:716-26
Schweppe, Devin K; Chavez, Juan D; Navare, Arti T et al. (2016) Spectral Library Searching To Identify Cross-Linked Peptides. J Proteome Res 15:1725-31

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