PDBsum entry 5a2e

Immune system

PDB id: 5a2e

Contents

Protein chain

303 a.a.

Ligands

NAG

EDO ×6

Waters ×43

PDB id:

5a2e

Name:

Immune system

Title:

Extracellular srcr domains of human cd6

Structure:

T-cell differentiation antigen cd6. Chain: a. Fragment: extracellular srcr domains. Synonym: t12, tp120, human cd6. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: cho lec 3.2.8.1. Expressed in: cricetulus griseus. Expression_system_taxid: 10029.

Resolution:

3.15Å R-factor: 0.255 R-free: 0.283

Authors:

P.E.Chappell,S.Johnson,S.M.Lea,M.H.Brown

Key ref:

P.E.Chappell et al. (2015). Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction. Structure, 23, 1426-1436. PubMed id: 26146185 DOI: 10.1016/j.str.2015.05.019

Date:

18-May-15 Release date: 22-Jul-15

Protein chain

P30203  (CD6_HUMAN) -  T-cell differentiation antigen CD6 from Homo sapiens

Seq: 668 a.a.

Struc: 303 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1016/j.str.2015.05.019

Structure 23:1426-1436 (2015)

PubMed id: 26146185

Structures of CD6 and Its Ligand CD166 Give Insight into Their Interaction.

P.E.Chappell, L.I.Garner, J.Yan, C.Metcalfe, D.Hatherley, S.Johnson, C.V.Robinson, S.M.Lea, M.H.Brown.

ABSTRACT

CD6 is a transmembrane protein with an extracellular region containing three scavenger receptor cysteine rich (SRCR) domains. The membrane proximal domain of CD6 binds the N-terminal immunoglobulin superfamily (IgSF) domain of another cell surface receptor, CD166, which also engages in homophilic interactions. CD6 expression is mainly restricted to T cells, and the interaction between CD6 and CD166 regulates T-cell activation. We have solved the X-ray crystal structures of the three SRCR domains of CD6 and two N-terminal domains of CD166. This first structure of consecutive SRCR domains reveals a nonlinear organization. We characterized the binding sites on CD6 and CD166 and showed that a SNP in CD6 causes glycosylation that hinders the CD6/CD166 interaction. Native mass spectrometry analysis showed that there is competition between the heterophilic and homophilic interactions. These data give insight into how interactions of consecutive SRCR domains are perturbed by SNPs and potential therapeutic reagents.