PDBsum entry 4nup

Cell adhesion

PDB id: 4nup

Contents

Protein chains

217 a.a.

Metals

_CA ×10

Waters ×576

PDB id:

4nup

Name:

Cell adhesion

Title:

Crystal structure of mouse n-cadherin ec1-2 with aa insertion between residues 2 and 3

Structure:

N-cadherin ec1-2. Chain: a, b, c. Fragment: unp residues 160-374. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: cdh2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.70Å R-factor: 0.175 R-free: 0.229

Authors:

X.Jin

Key ref:

J.Vendome et al. (2014). Structural and energetic determinants of adhesive binding specificity in type I cadherins. Proc Natl Acad Sci U S A, 111, E4175. PubMed id: 25253890 DOI: 10.1073/pnas.1416737111

Date:

03-Dec-13 Release date: 24-Sep-14

Protein chains

P15116  (CADH2_MOUSE) -  Cadherin-2 from Mus musculus

Seq: 906 a.a.

Struc: 217 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.1416737111

Proc Natl Acad Sci U S A 111:E4175 (2014)

PubMed id: 25253890

Structural and energetic determinants of adhesive binding specificity in type I cadherins.

J.Vendome, K.Felsovalyi, H.Song, Z.Yang, X.Jin, J.Brasch, O.J.Harrison, G.Ahlsen, F.Bahna, A.Kaczynska, P.S.Katsamba, D.Edmond, W.L.Hubbell, L.Shapiro, B.Honig.

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.