1G13

HUMAN GM2 ACTIVATOR STRUCTURE

1G13 の概要

• エントリーDOI: 10.2210/pdb1g13/pdb
• 分子名称: GANGLIOSIDE M2 ACTIVATOR PROTEIN, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• 機能のキーワード: beta cup, ligand binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Lysosome: P17900
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 53332.59

構造登録者

Wright, C.S.,Li, S.C.,Rastinejad, F. (登録日: 2000-10-10, 公開日: 2001-04-11, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)