1G13

HUMAN GM2 ACTIVATOR STRUCTURE

Summary for 1G13

• Entry DOI: 10.2210/pdb1g13/pdb
• Descriptor: GANGLIOSIDE M2 ACTIVATOR PROTEIN, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• Functional Keywords: beta cup, ligand binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P17900
• Total number of polymer chains: 3
• Total formula weight: 53332.59

Authors

Wright, C.S.,Li, S.C.,Rastinejad, F. (deposition date: 2000-10-10, release date: 2001-04-11, Last modification date: 2024-10-30)

Primary citation

Wright, C.S.,Li, S.C.,Rastinejad, F.
Crystal structure of human GM2-activator protein with a novel beta-cup topology.
J.Mol.Biol., 304:411-422, 2000

PubMed Abstract: GM2 activator protein (GM2-AP) belongs to a small group of non- enzymatic lysosomal proteins that act as cofactors in the sequential degradation of gangliosides. It has been postulated that GM2-AP extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-d-galactosamine and conversion to GM3. The high affinity of GM2-AP for GM2 is based on specfic recognition of the oligosaccharide moiety as well as the ceramide lipid tail. Genetic defects in GM2-AP result in an atypical form of Tay-Sachs disease known as variant AB GM2 gangliosidosis. The 2.0 A resolution crystal structure of GM2-AP reported here reveals a previously unobserved fold whose main feature is an eight-stranded cup-shaped anti-parallel beta-pleated sheet. The striking feature of the GM2-AP structure is that it possesses an accessible central hydrophobic cavity rather than a buried hydrophobic core. The dimensions of this cavity (12 Ax14 Ax22 A) are suitable for binding 18-carbon lipid acyl chains. Flexible surface loops and a short alpha-helix decorate the mouth of the beta-cup and may control lipid entry to the cavity.

PubMed: 11090283
DOI: 10.1006/jmbi.2000.4225

Experimental method

X-RAY DIFFRACTION (2 Å)