7cly | pdb_00007cly

Structure of the DOCK8 DHR-1 domain crystallized with di-C8-phosphatidylinositol-(4,5)-bisphosphate

spinqualitylabelsall models 7cly, resolution 1.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7cly is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.432Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DOCK8_MOUSE Potential guanine nucleotide exchange factor (GEF). GEF proteins activate some small GTPases by exchanging bound GDP for free GTP (By similarity). Publication Abstract from PubMed DOCK8 is a Cdc42-specific guanine-nucleotide exchange factor that is essential for development and functions of various subsets of leukocytes in innate and acquired immune responses. Although DOCK8 plays a critical role in spatial control of Cdc42 activity during interstitial leukocyte migration, the mechanism remains unclear. We show that the DOCK homology region (DHR)-1 domain of DOCK8 binds specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and is required for its recruitment to the plasma membrane. Structural and biochemical analyses reveal that DOCK8 DHR-1 domain consists of a C2 domain-like core with loops creating the upper surface pocket, where three basic residues are located for stereospecific recognition of phosphoinositides. Substitution of the two basic residues, K576 and R581, with alanine abolished PI(4,5)P2 binding in vitro, ablated the ability of DOCK8 to activate Cdc42 and support leukocyte migration in three-dimensional collagen gels. Dendritic cells carrying the mutation exhibited defective interstitial migration in vivo. Thus, our study uncovers a critical role of DOCK8 in coupling PI(4,5)P2 signaling with Cdc42 activation for immune regulation. A conserved PI(4,5)P2-binding domain is critical for immune regulatory function of DOCK8.,Sakurai T, Kukimoto-Niino M, Kunimura K, Yamane N, Sakata D, Aihara R, Yasuda T, Yokoyama S, Shirouzu M, Fukui Y, Uruno T Life Sci Alliance. 2021 Feb 11;4(4). pii: 4/4/e202000873. doi:, 10.26508/lsa.202000873. Print 2021 Apr. PMID:33574036 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dedicator of cytokinesis protein 3D structures

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