3RWV

Crystal Structure of apo-form of Human Glycolipid Transfer Protein at 1.5 A resolution

3RWV の概要

• エントリーDOI: 10.2210/pdb3rwv/pdb
• 関連するPDBエントリー: 1SWX 2EVT 3RIC 3RZN 3S0I 3S0K
• 分子名称: Glycolipid transfer protein, SULFATE ION (3 entities in total)
• 機能のキーワード: gltp-fold, lipid transport
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q9NZD2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47851.62

構造登録者

Samygina, V.,Cabo-Bilbao, A.,Popov, A.N.,Ochoa-Lizarralde, B.,Goni-de-Cerio, F.,Patel, D.J.,Brown, R.E.,Malinina, L. (登録日: 2011-05-09, 公開日: 2012-02-08, 最終更新日: 2024-02-28)

主引用文献

Samygina, V.R.,Popov, A.N.,Cabo-Bilbao, A.,Ochoa-Lizarralde, B.,Goni-de-Cerio, F.,Zhai, X.,Molotkovsky, J.G.,Patel, D.J.,Brown, R.E.,Malinina, L.
Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein.
Structure, 19:1644-1654, 2011

PubMed Abstract: Human glycolipid transfer protein (GLTP) fold represents a novel structural motif for lipid binding/transfer and reversible membrane translocation. GLTPs transfer glycosphingolipids (GSLs) that are key regulators of cell growth, division, surface adhesion, and neurodevelopment. Herein, we report structure-guided engineering of the lipid binding features of GLTP. New crystal structures of wild-type GLTP and two mutants (D48V and A47D‖D48V), each containing bound N-nervonoyl-sulfatide, reveal the molecular basis for selective anchoring of sulfatide (3-O-sulfo-galactosylceramide) by D48V-GLTP. Directed point mutations of "portal entrance" residues, A47 and D48, reversibly regulate sphingosine access to the hydrophobic pocket via a mechanism that could involve homodimerization. "Door-opening" conformational changes by phenylalanines within the hydrophobic pocket are revealed during lipid encapsulation by new crystal structures of bona fide apo-GLTP and GLTP complexed with N-oleoyl-glucosylceramide. The development of "engineered GLTPs" with enhanced specificity for select GSLs provides a potential new therapeutic approach for targeting GSL-mediated pathologies.

PubMed: 22078563
DOI: 10.1016/j.str.2011.09.011

実験手法

X-RAY DIFFRACTION (1.5 Å)