4Q95

Crystal structure of HRASLS3/LRAT chimeric protein

4Q95 の概要

• エントリーDOI: 10.2210/pdb4q95/pdb
• 関連するPDBエントリー: 4DOT
• 分子名称: HRAS-like suppressor 3, Lecithin retinol acyltransferase, HEPTANOIC ACID (3 entities in total)
• 機能のキーワード: lecithin:retinol acyltransferase, alpha/beta fold, acylation, membrane, transferase
• 由来する生物種: Homo sapiens (human, mouse); 詳細
• 細胞内の位置: Membrane ; Single-pass membrane protein : P53816
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34173.26

構造登録者

Golczak, M.,Kiser, P.D.,Sears, A.E.,Palczewski, K. (登録日: 2014-04-29, 公開日: 2014-10-29, 最終更新日: 2024-11-20)

主引用文献

Golczak, M.,Sears, A.E.,Kiser, P.D.,Palczewski, K.
LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3.
Nat.Chem.Biol., 11:26-32, 2015

PubMed Abstract: Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. Here, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-Å crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompanied by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. These findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family.

PubMed: 25383759
DOI: 10.1038/nchembio.1687

実験手法

X-RAY DIFFRACTION (2.2 Å)