1JWG

VHS Domain of human GGA1 complexed with cation-independent M6PR C-terminal Peptide

Summary for 1JWG

• Entry DOI: 10.2210/pdb1jwg/pdb
• Related: 1JWF
• Descriptor: ADP-ribosylation factor binding protein GGA1, Cation-independent mannose-6-phosphate receptor, IODIDE ION, ... (4 entities in total)
• Functional Keywords: super helix, protein-peptide complex, protein transport-protein binding complex, protein transport/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q9UJY5; Lysosome membrane; Single-pass type I membrane protein: P11717
• Total number of polymer chains: 4
• Total formula weight: 37479.45

Authors

Shiba, T.,Takatsu, H.,Nogi, T.,Matsugaki, N.,Kawasaki, M.,Igarashi, N.,Suzuki, M.,Kato, R.,Earnest, T.,Nakayama, K.,Wakatsuki, S. (deposition date: 2001-09-04, release date: 2002-03-06, Last modification date: 2024-10-09)

Primary citation

Shiba, T.,Takatsu, H.,Nogi, T.,Matsugaki, N.,Kawasaki, M.,Igarashi, N.,Suzuki, M.,Kato, R.,Earnest, T.,Nakayama, K.,Wakatsuki, S.
Structural basis for recognition of acidic-cluster dileucine sequence by GGA1.
Nature, 415:937-941, 2002

PubMed Abstract: 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.

PubMed: 11859376
DOI: 10.1038/415937a

Experimental method

X-RAY DIFFRACTION (2 Å)