PDBsum entry 4zmq

Cell adhesion

PDB id: 4zmq

Contents

Protein chains

200 a.a.

214 a.a.

Ligands

1PE

Metals

_CA ×8

Waters ×249

PDB id:

4zmq

Name:

Cell adhesion

Title:

Crystal structure of human p-cadherin (ss-x-dimer)

Structure:

Cadherin-3. Chain: a, b. Fragment: unp residues 108-320. Synonym: placental cadherin,p-cadherin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdh3, cdhp. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.189 R-free: 0.231

Authors:

J.M.M.Caaveiro,S.Kudo,K.Tsumoto

Key ref:

S.Kudo et al. (2016). Adhesive Dimerization of Human P-Cadherin Catalyzed by a Chaperone-like Mechanism. Structure, 24, 1523-1536. PubMed id: 27545624 DOI: 10.1016/j.str.2016.07.002

Date:

04-May-15 Release date: 07-Sep-16

Protein chain

P22223  (CADH3_HUMAN) -  Cadherin-3 from Homo sapiens

Seq: 829 a.a.

Struc: 200 a.a.*

Protein chain

P22223  (CADH3_HUMAN) -  Cadherin-3 from Homo sapiens

Seq: 829 a.a.

Struc: 214 a.a.*

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

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1016/j.str.2016.07.002

Structure 24:1523-1536 (2016)

PubMed id: 27545624

Adhesive Dimerization of Human P-Cadherin Catalyzed by a Chaperone-like Mechanism.

S.Kudo, J.M.Caaveiro, K.Tsumoto.

ABSTRACT

Orderly assembly of classical cadherins governs cell adhesion and tissue maintenance. A key event is the strand-swap dimerization of the extracellular ectodomains of two cadherin molecules from apposing cells. Here we have determined crystal structures of P-cadherin in six different conformational states to elaborate a motion picture of its adhesive dimerization at the atomic level. The snapshots revealed that cell-adhesive dimerization is facilitated by several intermediate states collectively termed X-dimer in analogy to other classical cadherins. Based on previous studies and on the combined structural, kinetic, thermodynamic, biochemical, and cellular data reported herein, we propose that the adhesive dimerization of human P-cadherin is achieved by a stepwise mechanism analogous to that of assembly chaperones. This mechanism, applicable to type I classical cadherins, confers high specificity and fast association rates. We expect these findings to guide innovative therapeutic approaches targeting P-cadherin in cancer.