1NA8

Crystal structure of ADP-ribosylation factor binding protein GGA1

Summary for 1NA8

• Entry DOI: 10.2210/pdb1na8/pdb
• Related: 1GYU 1NAF
• Descriptor: ADP-ribosylation factor binding protein GGA1 (2 entities in total)
• Functional Keywords: clathrin-adaptor, gga, appendage, beta-sandwich, signaling protein, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q9UJY5
• Total number of polymer chains: 2
• Total formula weight: 34706.42

Authors

Lui, W.W.,Collins, B.M.,Hirst, J.,Motley, A.,Millar, C.,Schu, P.,Owen, D.J.,Robinson, M.S. (deposition date: 2002-11-27, release date: 2003-07-29, Last modification date: 2023-08-16)

Primary citation

Lui, W.W.,Collins, B.M.,Hirst, J.,Motley, A.,Millar, C.,Schu, P.,Owen, D.J.,Robinson, M.S.
Binding partners for the COOH-terminal appendage domains of the GGAs and gamma-adaptin
Mol.Cell.Biol., 14:2385-23898, 2003

PubMed Abstract: The adaptor appendage domains are believed to act as binding platforms for coated vesicle accessory proteins. Using glutathione S-transferase pulldowns from pig brain cytosol, we find three proteins that can bind to the appendage domains of both the AP-1 gamma subunit and the GGAs: gamma-synergin and two novel proteins, p56 and p200. p56 elicited better antibodies than p200 and was generally more tractable. Although p56 and gamma-synergin bind to both GGA and gamma appendages in vitro, immunofluorescence labeling of nocodazole-treated cells shows that p56 colocalizes with GGAs on TGN46-positive membranes, whereas gamma-synergin colocalizes with AP-1 primarily on a different membrane compartment. Furthermore, in AP-1-deficient cells, p56 remains membrane-associated whereas gamma-synergin becomes cytosolic. Thus, p56 and gamma-synergin show very strong preferences for GGAs and AP-1, respectively, in vivo. However, the GGA and gamma appendages share the same fold as determined by x-ray crystallography, and mutagenesis reveals that the same amino acids contribute to their binding sites. By overexpressing wild-type GGA and gamma appendage domains in cells, we can drive p56 and gamma-synergin, respectively, into the cytosol, suggesting a possible mechanism for selectively disrupting the two pathways.

PubMed: 12808037
DOI: 10.1091/mbc.E02-11-0735

Experimental method

X-RAY DIFFRACTION (2.3 Å)