1SX6

Crystal structure of human Glycolipid Transfer protein in lactosylceramide-bound form

1SX6 の概要

• エントリーDOI: 10.2210/pdb1sx6/pdb
• 関連するPDBエントリー: 1SWX
• 関連するBIRD辞書のPRD_ID: PRD_900004
• 分子名称: Glycolipid transfer protein, beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, SPHINGOSINE, ... (6 entities in total)
• 機能のキーワード: glycosphingolipid transfer protein-lactosylceramide complex, lipid transport
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24916.26

構造登録者

Malinina, L.,Malakhova, M.L.,Teplov, A.,Brown, R.E.,Patel, D.J. (登録日: 2004-03-30, 公開日: 2004-08-31, 最終更新日: 2023-08-23)

主引用文献

Malinina, L.,Malakhova, M.L.,Teplov, A.,Brown, R.E.,Patel, D.J.
Structural basis for glycosphingolipid transfer specificity.
Nature, 430:1048-1053, 2004

PubMed Abstract: Lipid transfer proteins are important in membrane vesicle biogenesis and trafficking, signal transduction and immunological presentation processes. The conserved and ubiquitous mammalian glycolipid transfer proteins (GLTPs) serve as potential regulators of cell processes mediated by glycosphingolipids, ranging from differentiation and proliferation to invasive adhesion, neurodegeneration and apoptosis. Here we report crystal structures of apo-GLTP (1.65 A resolution) and lactosylceramide-bound (1.95 A) GLTP, in which the bound glycosphingolipid is sandwiched, after adaptive recognition, within a previously unknown two-layer all-alpha-helical topology. Glycosphingolipid binding specificity is achieved through recognition and anchoring of the sugar-amide headgroup to the GLTP recognition centre by hydrogen bond networks and hydrophobic contacts, and encapsulation of both lipid chains, in a precisely oriented manner within a 'moulded-to-fit' hydrophobic tunnel. A cleft-like conformational gating mechanism, involving two interhelical loops and one alpha-helix of GLTP, could enable the glycolipid chains to enter and leave the tunnel in the membrane-associated state. Mutation and functional analyses of residues in the glycolipid recognition centre and within the hydrophobic tunnel support a framework for understanding how GLTPs acquire and release glycosphingolipids during lipid intermembrane transfer and presentation processes.

PubMed: 15329726
DOI: 10.1038/nature02856

実験手法

X-RAY DIFFRACTION (1.95 Å)