7rx9 | pdb_00007rx9

Structure of autoinhibited P-Rex1

spinqualitylabelsall models 7rx9, resolution 3.22Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rx9 is a 1 chain structure with sequence from Escherichia virus T4 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.22Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer. PREX1_HUMAN Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils. Publication Abstract from PubMed P-Rex (PI(3,4,5)P3-dependent Rac exchanger) guanine nucleotide exchange factors potently activate Rho GTPases. P-Rex guanine nucleotide exchange factors are autoinhibited, synergistically activated by Gbetagamma and PI(3,4,5)P3 binding and dysregulated in cancer. Here, we use X-ray crystallography, cryogenic electron microscopy and crosslinking mass spectrometry to determine the structural basis of human P-Rex1 autoinhibition. P-Rex1 has a bipartite structure of N- and C-terminal modules connected by a C-terminal four-helix bundle that binds the N-terminal Pleckstrin homology (PH) domain. In the N-terminal module, the Dbl homology (DH) domain catalytic surface is occluded by the compact arrangement of the DH-PH-DEP1 domains. Structural analysis reveals a remarkable conformational transition to release autoinhibition, requiring a 126 degrees opening of the DH domain hinge helix. The off-axis position of Gbetagamma and PI(3,4,5)P3 binding sites further suggests a counter-rotation of the P-Rex1 halves by 90 degrees facilitates PH domain uncoupling from the four-helix bundle, releasing the autoinhibited DH domain to drive Rho GTPase signaling. Structure of the metastatic factor P-Rex1 reveals a two-layered autoinhibitory mechanism.,Chang YG, Lupton CJ, Bayly-Jones C, Keen AC, D'Andrea L, Lucato CM, Steele JR, Venugopal H, Schittenhelm RB, Whisstock JC, Halls ML, Ellisdon AM Nat Struct Mol Biol. 2022 Jul 21. pii: 10.1038/s41594-022-00804-9. doi:, 10.1038/s41594-022-00804-9. PMID:35864164 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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