5BRL

Crystal Structure of L124D STARD4

5BRL の概要

• エントリーDOI: 10.2210/pdb5brl/pdb
• 分子名称: StAR-related lipid transfer protein 4 (2 entities in total)
• 機能のキーワード: lipid binding protein, alpha helix grip
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48220.64

構造登録者

Iaea, D.B.,Dikiy, I.,Kiburu, I.,Eliezer, D.E.,Maxfield, F.R. (登録日: 2015-05-31, 公開日: 2015-07-22, 最終更新日: 2023-09-27)

主引用文献

Iaea, D.B.,Dikiy, I.,Kiburu, I.,Eliezer, D.,Maxfield, F.R.
STARD4 Membrane Interactions and Sterol Binding.
Biochemistry, 54:4623-4636, 2015

PubMed Abstract: The steroidogenic acute regulatory protein-related lipid transfer (START) domain family is defined by a conserved 210-amino acid sequence that folds into an α/β helix-grip structure. Members of this protein family bind a variety of ligands, including cholesterol, phospholipids, sphingolipids, and bile acids, with putative roles in nonvesicular lipid transport, metabolism, and cell signaling. Among the soluble START proteins, STARD4 is expressed in most tissues and has previously been shown to transfer sterol, but the molecular mechanisms of membrane interaction and sterol binding remain unclear. In this work, we use biochemical techniques to characterize regions of STARD4 and determine their role in membrane interaction and sterol binding. Our results show that STARD4 interacts with anionic membranes through a surface-exposed basic patch and that introducing a mutation (L124D) into the Omega-1 (Ω1) loop, which covers the sterol binding pocket, attenuates sterol transfer activity. To gain insight into the attenuating mechanism of the L124D mutation, we conducted structural and biophysical studies of wild-type and L124D STARD4. These studies show that the L124D mutation reduces the conformational flexibility of the protein, resulting in a diminished level of membrane interaction and sterol transfer. These studies also reveal that the C-terminal α-helix, and not the Ω1 loop, partitions into the membrane bilayer. On the basis of these observations, we propose a model of STARD4 membrane interaction and sterol binding and release that requires dynamic movement of both the Ω1 loop and membrane insertion of the C-terminal α-helix.

PubMed: 26168008
DOI: 10.1021/acs.biochem.5b00618

実験手法

X-RAY DIFFRACTION (2.003 Å)