1jwg
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VHS Domain of human GGA1 complexed with cation-independent M6PR C-terminal Peptide
OverviewOverview
GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-interacting, proteins) are critical for the transport of soluble proteins from the, trans-Golgi network (TGN) to endosomes/lysosomes by means of interactions, with TGN-sorting receptors, ADP-ribosylation factor (ARF), and clathrin., The amino-terminal VHS domains of GGAs form complexes with the cytoplasmic, domains of sorting receptors by recognizing acidic-cluster dileucine, (ACLL) sequences. Here we report the X-ray structure of the GGA1 VHS, domain alone, and in complex with the carboxy-terminal peptide of, cation-independent mannose 6-phosphate receptor containing an ACLL, sequence. The VHS domain forms a super helix with eight alpha-helices, similar to the VHS domains of TOM1 and Hrs. Unidirectional movements of, helices alpha6 and alpha8, and some of their side chains, create a set of, electrostatic and hydrophobic interactions for correct recognition of the, ACLL peptide. This recognition mechanism provides the basis for regulation, of protein transport from the TGN to endosomes/lysosomes, which is shared, by sortilin and low-density lipoprotein receptor-related protein.
DiseaseDisease
Known diseases associated with this structure: Hepatocellular carcinoma OMIM:[147280]
About this StructureAbout this Structure
1JWG is a Protein complex structure of sequences from Homo sapiens with IOD as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for recognition of acidic-cluster dileucine sequence by GGA1., Shiba T, Takatsu H, Nogi T, Matsugaki N, Kawasaki M, Igarashi N, Suzuki M, Kato R, Earnest T, Nakayama K, Wakatsuki S, Nature. 2002 Feb 21;415(6874):937-41. PMID:11859376
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