2VKW

Human NCAM, FN3 domains 1 and 2

2VKW の概要

• エントリーDOI: 10.2210/pdb2vkw/pdb
• 関連するPDBエントリー: 2VKX
• 分子名称: NEURAL CELL ADHESION MOLECULE 1,140 KDA ISOFORM, SULFATE ION (3 entities in total)
• 機能のキーワード: adhesion receptor, cell adhesion
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46683.87

構造登録者

Carafoli, F.,Saffell, J.L.,Hohenester, E. (登録日: 2008-01-04, 公開日: 2008-02-26, 最終更新日: 2024-05-08)

主引用文献

Carafoli, F.,Saffell, J.L.,Hohenester, E.
Structure of the Tandem Fibronectin Type 3 Domains of Neural Cell Adhesion Molecule
J.Mol.Biol., 377:524-, 2008

PubMed Abstract: Activation of the fibroblast growth factor receptor (FGFR) by neural cell adhesion molecule (NCAM) is essential for NCAM-mediated neurite outgrowth. Previous peptide studies have identified two regions in the fibronectin type 3 (FN3)-like domains of NCAM as being important for these activities. Here we report the crystal structure of the NCAM FN3 domain tandem, which reveals an acutely bent domain arrangement. Mutation of a non-conserved surface residue (M610R) led to a second crystal form showing a substantially different conformation. Thus, the FN3 domain linker is highly flexible, suggesting that it corresponds to the hinge seen in electron micrographs of NCAM. The two putative FGFR1-binding segments, one in each NCAM FN3 domain, are situated close to the domain interface. They form a contiguous patch in the more severely bent conformation but become separated upon straightening of the FN3 tandem, suggesting that conformational changes within NCAM may modulate FGFR1 activation. Surface plasmon resonance experiments demonstrated only a very weak interaction between the NCAM FN3 tandem and soluble FGFR1 proteins expressed in mammalian cells (dissociation constant >100 muM). Thus, the NCAM-FGFR1 interaction at the cell surface is likely to depend upon avidity effects due to receptor clustering.

PubMed: 18261743
DOI: 10.1016/J.JMB.2008.01.030

実験手法

X-RAY DIFFRACTION (2.3 Å)