4F1P

Crystal Structure of mutant S554D for ArfGAP and ANK repeat domain of ACAP1

Summary for 4F1P

• Entry DOI: 10.2210/pdb4f1p/pdb
• Related: 3JUE 3T9K
• Descriptor: Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1, ZINC ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: arfgap domain, ank repeat, zinc-binding module, protein transport
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 78699.89

Authors

Sun, F.,Pang, X.,Zhang, K.,Ma, J.,Zhou, Q. (deposition date: 2012-05-07, release date: 2012-07-18, Last modification date: 2024-03-20)

Primary citation

Bai, M.,Pang, X.,Lou, J.,Zhou, Q.,Zhang, K.,Ma, J.,Li, J.,Sun, F.,Hsu, V.W.
Mechanistic insights into regulated cargo binding by ACAP1 protein
J.Biol.Chem., 287:28675-28685, 2012

PubMed Abstract: Coat complexes sort protein cargoes into vesicular transport pathways. An emerging class of coat components has been the GTPase-activating proteins (GAPs) that act on the ADP-ribosylation factor (ARF) family of small GTPases. ACAP1 (ArfGAP with coiled-coil, ankyrin repeat, and PH domains protein 1) is an ARF6 GAP that also acts as a key component of a recently defined clathrin complex for endocytic recycling. Phosphorylation by Akt has been shown to enhance cargo binding by ACAP1 in explaining how integrin recycling is an example of regulated transport. We now shed further mechanistic insights into how this regulation is achieved at the level of cargo binding by ACAP1. We initially defined a critical sequence in the cytoplasmic domain of integrin β1 recognized by ACAP1 and showed that this sequence acts as a recycling sorting signal. We then pursued a combination of structural, modeling, and functional studies, which suggest that phosphorylation of ACAP1 relieves a localized mechanism of autoinhibition in regulating cargo binding. Thus, we have elucidated a key regulatory juncture that controls integrin recycling and also advanced the understanding of how regulated cargo binding can lead to regulated transport.

PubMed: 22645133
DOI: 10.1074/jbc.M112.378810

Experimental method

X-RAY DIFFRACTION (2.3 Å)