1g13
From Proteopedia
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HUMAN GM2 ACTIVATOR STRUCTURE
Contents |
Overview
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.
Disease
Known disease associated with this structure: GM2-gangliosidosis, AB variant OMIM:[272750]
About this Structure
1G13 is a Single protein structure of sequence from Homo sapiens with EPE as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of human GM2-activator protein with a novel beta-cup topology., Wright CS, Li SC, Rastinejad F, J Mol Biol. 2000 Dec 1;304(3):411-22. PMID:11090283
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