3G2S

VHS Domain of human GGA1 complexed with SorLA C-terminal Peptide

Summary for 3G2S

• Entry DOI: 10.2210/pdb3g2s/pdb
• Related: 3G2T 3G2U 3G2V 3G2W
• Descriptor: ADP-ribosylation factor-binding protein GGA1, C-terminal fragment of Sortilin-related receptor, HEXANE-1,6-DIOL, ... (4 entities in total)
• Functional Keywords: adp-ribosylation factor binding protein gga1, vhs, acidic-cluster dileucine signal, sorla, protein transport
• Biological source: Homo sapiens (human); More
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q9UJY5; Membrane; Single-pass type I membrane protein (Potential): Q92673
• Total number of polymer chains: 4
• Total formula weight: 36764.43

Authors

Cramer, J.F.,Behrens, M.A.,Gustafsen, C.,Oliveira, C.L.P.,Pedersen, J.S.,Madsen, P.,Petersen, C.M.,Thirup, S.S. (deposition date: 2009-02-01, release date: 2009-12-15, Last modification date: 2024-11-06)

Primary citation

Cramer, J.F.,Gustafsen, C.,Behrens, M.A.,Oliveira, C.L.P.,Pedersen, J.S.,Madsen, P.,Petersen, C.M.,Thirup, S.S.
GGA autoinhibition revisited
Traffic, 11:259-273, 2010

PubMed Abstract: The cytosolic adaptors GGA1-3 mediate sorting of transmembrane proteins displaying a C-terminal acidic dileucine motif (DXXLL) in their cytosolic domain. GGA1 and GGA3 contain similar but intrinsic motifs that are believed to serve as autoinhibitory sites activated by the phosphorylation of a serine positioned three residues upstream of the DXXLL motif. In the present study, we have subjected the widely acknowledged concept of GGA1 autoinhibition to a thorough structural and functional examination. We find that (i) the intrinsic motif of GGA1 is inactive, (ii) only C-terminal DXXLL motifs constitute active GGA binding sites, (iii) while aspartates and phosphorylated serines one or two positions upstream of the DXXLL motif increase GGA1 binding, phosphoserines further upstream have little or no influence and (iv) phosphorylation of GGA1 does not affect its conformation or binding to Sortilin and SorLA. Taken together, our findings seem to refute the functional significance of GGA autoinhibition in particular and of intrinsic GGA binding motifs in general.

PubMed: 20015111
DOI: 10.1111/j.1600-0854.2009.01017.x

Experimental method

X-RAY DIFFRACTION (1.7 Å)