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Structure of human ARL1 in complex with the DCB domain of BIG1Structure of human ARL1 in complex with the DCB domain of BIG1
Structural highlights
FunctionBIG1_HUMAN Promotes guanine-nucleotide exchange on ARF1 and ARF3. Promotes the activation of ARF1/ARF3 through replacement of GDP with GTP. Involved in vesicular trafficking. Required for the maintenance of Golgi structure; the function may be independent of its GEF activity. Required for the maturaion of integrin beta-1 in the Golgi. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. Inhibits GAP activity of MYO9B probably through competetive RhoA binding. The function in the nucleus remains to be determined.[1] [2] [3] [4] [5] Publication Abstract from PubMedThe GTPase Arf1 is the major regulator of vesicle traffic at both the cis- and trans-Golgi. Arf1 is activated at the cis-Golgi by the guanine nucleotide exchange factor (GEF) GBF1 and at the trans-Golgi by the related GEF BIG1 or its paralog, BIG2. The trans-Golgi-specific targeting of BIG1 and BIG2 depends on the Arf-like GTPase Arl1. We find that Arl1 binds to the dimerization and cyclophilin binding (DCB) domain in BIG1 and report a crystal structure of human Arl1 bound to this domain. Residues in the DCB domain that bind Arl1 are required for BIG1 to locate to the Golgi in vivo. DCB domain-binding residues in Arl1 have a distinct conformation from those in known Arl1-effector complexes, and this plasticity allows Arl1 to interact with different effectors of unrelated structure. The findings provide structural insight into how Arf1 GEFs, and hence active Arf1, achieve their correct subcellular distribution. Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi.,Galindo A, Soler N, McLaughlin SH, Yu M, Williams RL, Munro S Cell Rep. 2016 Jun 29. pii: S2211-1247(16)30762-8. doi:, 10.1016/j.celrep.2016.06.022. PMID:27373159[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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