6x1g

Crystal structure of a GEF domain from the Orientia tsutsugamushi protein OtDUB in complex with Rac1

spinqualitylabelsall models 6x1g, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6x1g is a 4 chain structure with sequence from Homo sapiens and Orientia tsutsugamushi str. Ikeda. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B3CVM3_ORITI Publication Abstract from PubMed Rho family GTPases regulate an array of cellular processes and are often modulated by pathogens to promote infection. Here, we identify a cryptic guanine nucleotide exchange factor (GEF) domain in the OtDUB protein encoded by the pathogenic bacterium Orientia tsutsugamushi A proteomics-based OtDUB interaction screen identified numerous potential host interactors, including the Rho GTPases Rac1 and Cdc42. We discovered a domain in OtDUB with Rac1/Cdc42 GEF activity (OtDUBGEF), with higher activity toward Rac1 in vitro. While this GEF bears no obvious sequence similarity to known GEFs, crystal structures of OtDUBGEF alone (3.0 A) and complexed with Rac1 (1.7 A) reveal striking convergent evolution, with a unique topology, on a V-shaped bacterial GEF fold shared with other bacterial GEF domains. Structure-guided mutational analyses identified residues critical for activity and a mechanism for nucleotide displacement. Ectopic expression of OtDUB activates Rac1 preferentially in cells, and expression of the OtDUBGEF alone alters cell morphology. Cumulatively, this work reveals a bacterial GEF within the multifunctional OtDUB that co-opts host Rac1 signaling to induce changes in cytoskeletal structure. Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi.,Lim C, Berk JM, Blaise A, Bircher J, Koleske AJ, Hochstrasser M, Xiong Y Proc Natl Acad Sci U S A. 2020 Nov 12. pii: 2018163117. doi:, 10.1073/pnas.2018163117. PMID:33184172 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Rac 3D structures

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