4NQQ

Crystal structure of mouse P-cadherin extracellular domains EC1-EC2

4NQQ の概要

• エントリーDOI: 10.2210/pdb4nqq/pdb
• 分子名称: Cadherin-3, CALCIUM ION, COPPER (II) ION, ... (4 entities in total)
• 機能のキーワード: extracellular cadherin (ec) domain, cell-cell adhesion, cell adhesion
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P10287
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95057.92

構造登録者

Brasch, J.,Shapiro, L. (登録日: 2013-11-25, 公開日: 2014-09-24, 最終更新日: 2023-09-20)

主引用文献

Vendome, J.,Felsovalyi, K.,Song, H.,Yang, Z.,Jin, X.,Brasch, J.,Harrison, O.J.,Ahlsen, G.,Bahna, F.,Kaczynska, A.,Katsamba, P.S.,Edmond, D.,Hubbell, W.L.,Shapiro, L.,Honig, B.
Structural and energetic determinants of adhesive binding specificity in type I cadherins.
Proc.Natl.Acad.Sci.USA, 111:E4175-E4184, 2014

PubMed Abstract: Type I cadherin cell-adhesion proteins are similar in sequence and structure and yet are different enough to mediate highly specific cell-cell recognition phenomena. It has previously been shown that small differences in the homophilic and heterophilic binding affinities of different type I family members can account for the differential cell-sorting behavior. Here we use a combination of X-ray crystallography, analytical ultracentrifugation, surface plasmon resonance and double electron-electron resonance (DEER) electron paramagnetic resonance spectroscopy to identify the molecular determinants of type I cadherin dimerization affinities. Small changes in sequence are found to produce subtle structural and dynamical changes that impact relative affinities, in part via electrostatic and hydrophobic interactions, and in part through entropic effects because of increased conformational heterogeneity in the bound states as revealed by DEER distance mapping in the dimers. These findings highlight the remarkable ability of evolution to exploit a wide range of molecular properties to produce closely related members of the same protein family that have affinity differences finely tuned to mediate their biological roles.

PubMed: 25253890
DOI: 10.1073/pnas.1416737111

実験手法

X-RAY DIFFRACTION (3.2 Å)