1PUB

GM2-activator Protein crystal structure

1PUB の概要

• エントリーDOI: 10.2210/pdb1pub/pdb
• 関連するPDBエントリー: 1G13 1PU5
• 分子名称: GM2-activator protein, 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE (3 entities in total)
• 機能のキーワード: beta-cup, enlarge lipid binding pocket, lipid 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: 1
• 化学式量合計: 18309.30

構造登録者

Wright, C.S.,Zhao, Q.,Rastinejad, F. (登録日: 2003-06-24, 公開日: 2004-06-29, 最終更新日: 2024-11-20)

主引用文献

Wright, C.S.,Zhao, Q.,Rastinejad, F.
Structural analysis of lipid complexes of GM2-activator protein.
J.Mol.Biol., 331:951-964, 2003

PubMed Abstract: The GM2-activator protein (GM2-AP) is a small lysosomal lipid transfer protein essential for the hydrolytic conversion of ganglioside GM2 to GM3 by beta-hexosaminidase A. The crystal structure of human apo-GM2-AP is known to consist of a novel beta-cup fold with a spacious hydrophobic interior. Here, we present two new structures of GM2-AP with bound lipids, showing two different lipid-binding modes within the apolar pocket. The 1.9A structure with GM2 bound shows the position of the ceramide tail and significant conformational differences among the three molecular copies in the asymmetric unit. The tetrasaccharide head group is not visible and is presumed to be disordered. However, its general position could be established through modeling. The structure of a low-pH crystal, determined at 2.5A resolution, has a significantly enlarged hydrophobic channel that merges with the apolar pocket. Electron density inside the pocket and channel suggests the presence of a trapped phospholipid molecule. Structure alignments among the four crystallographically unique monomers provide information on the potential role for lipid binding of flexible chain segments at the rim of the cavity opening. Two discrete orientations of the S130-T133 loop define an open and a closed configuration of the hydrophobic channel that merges with the apolar pocket. We propose: (i) that the low-pH structure represents an active membrane-binding conformation; (ii) that the mobile S130-T133 loop serves as a gate for passage of ligand into the apolar pocket; and (iii) that this loop and the adjacent apolar V59-W63 loop form a surface patch with two exposed tryptophan residues that could interface with lipid bilayers.

PubMed: 12909021
DOI: 10.1016/S0022-2836(03)00794-0

実験手法

X-RAY DIFFRACTION (2.51 Å)