1jpl
GGA3 VHS domain complexed with C-terminal peptide from cation-independent mannose 6-phosphate receptorGGA3 VHS domain complexed with C-terminal peptide from cation-independent mannose 6-phosphate receptor
Structural highlights
Function[GGA3_HUMAN] Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif.[1] [MPRI_HUMAN] Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation, by binding DPP4.[2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSpecific sorting signals direct transmembrane proteins to the compartments of the endosomal-lysosomal system. Acidic-cluster-dileucine signals present within the cytoplasmic tails of sorting receptors, such as the cation-independent and cation-dependent mannose-6-phosphate receptors, are recognized by the GGA (Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding) proteins. The VHS (Vps27p, Hrs and STAM) domains of the GGA proteins are responsible for the highly specific recognition of these acidic-cluster-dileucine signals. Here we report the structures of the VHS domain of human GGA3 complexed with signals from both mannose-6-phosphate receptors. The signals bind in an extended conformation to helices 6 and 8 of the VHS domain. The structures highlight an Asp residue separated by two residues from a dileucine sequence as critical recognition elements. The side chains of the Asp-X-X-Leu-Leu sequence interact with subsites consisting of one electropositive and two shallow hydrophobic pockets, respectively. The rigid spatial alignment of the three binding subsites leads to high specificity. Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains.,Misra S, Puertollano R, Kato Y, Bonifacino JS, Hurley JH Nature. 2002 Feb 21;415(6874):933-7. PMID:11859375[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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