4yon | pdb_00004yon

P-Rex1:Rac1 complex

spinqualitylabelsall models 4yon, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4yon is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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 The P-Rex (phosphatidylinositol(3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion and metastasis in several human cancers. The family is unique among Rho GEFs as their activity is regulated by the synergistic binding of PIP3 and Gbetagamma at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 A crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1:Rac1 interface reveal a critical role of this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. Structural data indicate the PIP3/Gbetagamma binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gbetagamma releases inhibitory C-terminal domains to expose the Rac1 binding site. The Phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac Exchanger 1:Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1:Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells.,Lucato CM, Halls ML, Ooms LM, Liu HJ, Mitchell CA, Whisstock JC, Ellisdon AM J Biol Chem. 2015 Jun 24. pii: jbc.M115.660456. PMID:26112412 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Rac 3D structures

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