5h3d
From Proteopedia
Helical structure of membrane tubules decorated by ACAP1 (BARPH doamin) protein by cryo-electron microscopy and MD simulation
Structural highlights
FunctionACAP1_HUMAN GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface. Required for regulated export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration.[1] [2] [3] [4] [5] Publication Abstract from PubMedStudies on the Bin-Amphiphysin-Rvs (BAR) domain have advanced a fundamental understanding of how proteins deform membrane. We previously showed that a BAR domain in tandem with a Pleckstrin Homology (PH domain) underlies the assembly of ACAP1 (Arfgap with Coil-coil, Ankryin repeat, and PH domain I) into an unusual lattice structure that also uncovers a new paradigm for how a BAR protein deforms membrane. Here, we initially pursued computation-based refinement of the ACAP1 lattice to identify its critical protein contacts. Simulation studies then revealed how ACAP1, which dimerizes into a symmetrical structure in solution, is recruited asymmetrically to the membrane through dynamic behavior. We also pursued electron microscopy (EM)-based structural studies, which shed further insight into the dynamic nature of the ACAP1 lattice assembly. As ACAP1 is an unconventional BAR protein, our findings broaden the understanding of the mechanistic spectrum by which proteins assemble into higher-ordered structures to achieve membrane deformation. ACAP1 assembles into an unusual protein lattice for membrane deformation through multiple stages.,Chan C, Pang X, Zhang Y, Niu T, Yang S, Zhao D, Li J, Lu L, Hsu VW, Zhou J, Sun F, Fan J PLoS Comput Biol. 2019 Jul 10;15(7):e1007081. doi: 10.1371/journal.pcbi.1007081. , eCollection 2019 Jul. PMID:31291238[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Chan C | Fan J | Pang XY | Sun F | Zhang Y
