6ixf
Crystal structure of SeMet apo SH3BP5 (P41)
Structural highlights
Function3BP5_HUMAN Inhibits the auto- and transphosphorylation activity of BTK. Plays a negative regulatory role in BTK-related cytoplasmic signaling in B-cells. May be involved in BCR-induced apoptotic cell death.[1] [2] Publication Abstract from PubMedThe Rab GTPase family is a major regulator of membrane traffic in eukaryotic cells. The Rab11 subfamily plays important roles in specific trafficking events such as exocytosis, endosomal recycling, and cytokinesis. SH3BP5 and SH3BP5-like (SH3BP5L) proteins have recently been found to serve as guanine nucleotide exchange factors (GEF) for Rab11. Here, we report the crystal structures of the SH3BP5 GEF domain alone and its complex with Rab11a. SH3BP5 exhibits a V-shaped structure comprising two coiled coils. The coiled coil composed of alpha1, and alpha4 is solely responsible for the Rab11a binding and GEF activity. SH3BP5 pulls out and deforms switch I of Rab11a so as to facilitate the GDP release from Rab11a. SH3BP5 interacts with the N-terminal region, switch I, interswitch, and switch II of Rab11a. SH3BP5 and SH3BP5L localize to Rab11-positive recycling endosomes and show GEF activity for all of the Rab11 family but not for Rab14. Fluorescence-based GEF assays combined with site-directed mutagenesis reveal the essential interactions between SH3BP5 and Rab11 family proteins for the GEF reaction on recycling endosomes. Structural basis of guanine nucleotide exchange for Rab11 by SH3BP5.,Goto-Ito S, Morooka N, Yamagata A, Sato Y, Sato K, Fukai S Life Sci Alliance. 2019 Mar 14;2(2). pii: 2/2/e201900297. doi:, 10.26508/lsa.201900297. Print 2019 Apr. PMID:30872413[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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