3CFW

L-selectin lectin and EGF domains

3CFW の概要

• エントリーDOI: 10.2210/pdb3cfw/pdb
• 関連するPDBエントリー: 1ESL 1G1Q 1G1R 1G1S 1G1T
• 分子名称: L-selectin, alpha-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: l-selectin, lectin, egf, cell adhesion, egf-like domain, glycoprotein, membrane, sushi, transmembrane
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P14151
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20381.64

構造登録者

Mehta, P.,Oganesyan, V.,Terzyan, S.,Mather, T.,McEver, R.P. (登録日: 2008-03-04, 公開日: 2008-03-18, 最終更新日: 2024-11-20)

主引用文献

Mehta-D'souza, P.,Klopocki, A.G.,Oganesyan, V.,Terzyan, S.,Mather, T.,Li, Z.,Panicker, S.R.,Zhu, C.,McEver, R.P.
Glycan Bound to the Selectin Low Affinity State Engages Glu-88 to Stabilize the High Affinity State under Force.
J.Biol.Chem., 292:2510-2518, 2017

PubMed Abstract: Selectin interactions with fucosylated glycan ligands mediate leukocyte rolling in the vasculature under shear forces. Crystal structures of P- and E-selectin suggest a two-state model in which ligand binding to the lectin domain closes loop 83-89 around the Ca coordination site, enabling Glu-88 to engage Ca and fucose. This triggers further allostery that opens the lectin/EGF domain hinge. The model posits that force accelerates transition from the bent (low affinity) to the extended (high affinity) state. However, transition intermediates have not been described, and the role of Glu-88 in force-assisted allostery has not been examined. Here we report the structure of the lectin and EGF domains of L-selectin bound to a fucose mimetic; that is, a terminal mannose on an -glycan attached to a symmetry-related molecule. The structure is a transition intermediate where loop 83-89 closes to engage Ca and mannose without triggering allostery that opens the lectin/EGF domain hinge. We used three complementary assays to compare ligand binding to WT selectins and to E88D selectins that replaced Glu-88 with Asp. Soluble P-selectinE88D bound with an ∼9-fold lower affinity to PSGL-1, a physiological ligand, due to faster dissociation. Adhesion frequency experiments with a biomembrane force probe could not detect interactions of P-selectinE88D with PSGL-1. Cells expressing transmembrane P-selectinE88D or L-selectinE88D detached from immobilized ligands immediately after initiating flow. Cells expressing E-selectinE88D rolled but detached faster. Our data support a two-state model for selectins in which Glu-88 must engage ligand to trigger allostery that stabilizes the high affinity state under force.

PubMed: 28011641
DOI: 10.1074/jbc.M116.767186

実験手法

X-RAY DIFFRACTION (2.2 Å)