2HBP

Solution Structure of Sla1 Homology Domain 1

2HBP の概要

• エントリーDOI: 10.2210/pdb2hbp/pdb
• 分子名称: Cytoskeleton assembly control protein SLA1 (1 entity in total)
• 機能のキーワード: sla1, shd1, npfx(1, 2)d, endocytosis, protein binding
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• 細胞内の位置: Nucleus: P32790
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7452.61

構造登録者

Overduin, M.,Mahadev, R.K. (登録日: 2006-06-14, 公開日: 2007-04-10, 最終更新日: 2024-05-29)

主引用文献

Mahadev, R.K.,Di Pietro, S.M.,Olson, J.M.,Piao, H.L.,Payne, G.S.,Overduin, M.
Structure of Sla1p homology domain 1 and interaction with the NPFxD endocytic internalization motif.
Embo J., 26:1963-1971, 2007

PubMed Abstract: Adaptor proteins play important endocytic roles including recognition of internalization signals in transmembrane cargo. Sla1p serves as the adaptor for uptake of transmembrane proteins containing the NPFxD internalization signal, and is essential for normal functioning of the actin cytoskeleton during endocytosis. The Sla1p homology domain 1 (SHD1) within Sla1p is responsible for recognition of the NPFxD signal. This study presents the NMR structure of the NPFxD-bound state of SHD1 and a model for the protein-ligand complex. The alpha+beta structure of the protein reveals an SH3-like topology with a solvent-exposed hydrophobic ligand binding site. NMR chemical shift perturbations and effects of structure-based mutations on ligand binding in vitro define residues that are key for NPFxD binding. Mutations that abolish ligand recognition in vitro also abolish NPFxD-mediated receptor internalization in vivo. Thus, SHD1 is a novel functional domain based on SH3-like topology, which employs a unique binding site to recognize the NPFxD endocytic internalization signal. Its distant relationship with the SH3 fold endows this superfamily with a new role in endocytosis.

PubMed: 17363896
DOI: 10.1038/sj.emboj.7601646

実験手法

SOLUTION NMR