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High-resolution protein complexes from integrating genomic information with molecular simulation.

TitleHigh-resolution protein complexes from integrating genomic information with molecular simulation.
Publication TypeJournal Article
Year of Publication2009
AuthorsSchug, A, Weigt, M, Onuchic, JN, Hwa, T, Szurmant, H
JournalProc Natl Acad Sci U S A
Volume106
Issue52
Pagination22124-9
Date Published2009 Dec 29
ISSN1091-6490
KeywordsAmino Acid Sequence, Bacterial Proteins, Biophysical Phenomena, Computer Simulation, Crystallography, X-Ray, Genomics, Intracellular Signaling Peptides and Proteins, Models, Molecular, Molecular Sequence Data, Multiprotein Complexes, Protein Kinases, Sequence Alignment, Thermodynamics, Thermotoga maritima
Abstract

Bacteria use two-component signal transduction systems (TCS) extensively to sense and react to external stimuli. In these, a membrane-bound sensor histidine kinase (SK) autophosphorylates in response to an environmental stimulus and transfers the phosphoryl group to a transcription factor/response regulator (RR) that mediates the cellular response. The complex between these two proteins is ruled by transient interactions, which provides a challenge to experimental structure determination techniques. The functional and structural homolog of an SK/RR pair Spo0B/Spo0F, however, has been structurally resolved. Here, we describe a method capable of generating structural models of such transient protein complexes. By using existing structures of the individual proteins, our method combines bioinformatically derived contact residue information with molecular dynamics simulations. We find crystal resolution accuracy with existing crystallographic data when reconstituting the known system Spo0B/Spo0F. Using this approach, we introduce a complex structure of TM0853/TM0468 as an exemplary SK/RR TCS, consistent with all experimentally available data.

DOI10.1073/pnas.0912100106
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID20018738
PubMed Central IDPMC2799721
Grant List019416 / / PHS HHS / United States
R01GM077298 / GM / NIGMS NIH HHS / United States