PDBsum entry 2wng

Cell adhesion

PDB id: 2wng

Contents

Protein chain

307 a.a. *

Ligands

NAG

Waters ×49

* Residue conservation analysis

PDB id:

2wng

Name:

Cell adhesion

Title:

Complete extracellular structure of human signal regulatory protein (sirp) alpha

Structure:

Tyrosine-protein phosphatase non-receptor type substrate 1. Chain: a. Fragment: ectodomain, residues 31-319. Synonym: shp substrate 1, shps-1, inhibitory receptor shps-1, signal- regulatory protein alpha-1, sirp-alpha-2, sirp-alpha-3, myd-1 antigen, brain ig-like molecule with tyrosine-based activation motifs, macrophage fusion receptor, cd172 antigen-like family member a, bit, sirp-alpha-1 human signal regulatory protein alpha. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_variant: lec3.2.8.1. Expression_system_cell_line: cho.

Resolution:

2.49Å R-factor: 0.221 R-free: 0.271

Authors:

D.Hatherley,S.C.Graham,K.Harlos,D.I.Stuart,A.N.Barclay

Key ref:

D.Hatherley et al. (2009). Structure of signal-regulatory protein alpha: a link to antigen receptor evolution. J Biol Chem, 284, 26613-26619. PubMed id: 19628875 DOI: 10.1074/jbc.M109.017566

Date:

09-Jul-09 Release date: 21-Jul-09

Protein chain

P78324  (SHPS1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type substrate 1 from Homo sapiens

Seq: 504 a.a.

Struc: 307 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

DOI no: 10.1074/jbc.M109.017566

J Biol Chem 284:26613-26619 (2009)

PubMed id: 19628875

Structure of signal-regulatory protein alpha: a link to antigen receptor evolution.

D.Hatherley, S.C.Graham, K.Harlos, D.I.Stuart, A.N.Barclay.

ABSTRACT

Signal-regulatory protein alpha (SIRPalpha) is a myeloid membrane receptor that interacts with the membrane protein CD47, a marker of self. We have solved the structure of the complete extracellular portion of SIRPalpha, comprising three immunoglobulin superfamily domains, by x-ray crystallography to 2.5 A resolution. These data, together with previous data on the N-terminal domain and its ligand CD47 (possessing a single immunoglobulin superfamily domain), show that the CD47-SIRPalpha interaction will span a distance of around 14 nm between interacting cells, comparable with that of an immunological synapse. The N-terminal (V-set) domain mediates binding to CD47, and the two others are found to be constant (C1-set) domains. C1-set domains are restricted to proteins involved in vertebrate antigen recognition: T cell antigen receptors, immunoglobulins, major histocompatibility complex antigens, tapasin, and beta2-microglobulin. The domains of SIRPalpha (domains 2 and 3) are structurally more similar to C1-set domains than any cell surface protein not involved in antigen recognition. This strengthens the suggestion from sequence analysis that SIRP is evolutionarily closely related to antigen recognition proteins.

Selected figure(s)

Figure 3.
Model for the CD47-SIRPα complex formed between interacting cells. The entire extracellular CD47-SIRPα complex, modeled by superposing the structure of SIRPα domains 1–3 onto the structure of CD47 in complex with SIRPα domain 1 (5), is shown as a blue (SIRPα) and yellow (CD47) molecular surface. Schematic representations of the five transmembrane helices of CD47 (yellow cylinders) and single transmembrane helix of SIRPα (blue cylinder) are shown. The regions between transmembrane helices and resolved structures for CD47 and SIRPα are illustrated as dotted lines. The location of CD47 residue Cys^15, which forms a disulfide bond with Cys^245 (proposed to reside in the extracellular loop between transmembrane helices 4 and 5), is highlighted in red.

Figure 5.
Similarity of SIRPα domains to IgSF V- and C1-set domains. SSM superposition Cα r.m.s. deviations for query domain structures versus the IgSF SCOP families used to generate Table 2 are shown as frequency histograms in A for the V-set (b.1.1.1) and in B for the C1-set (b.1.1.2). Frequency intervals of 0.2 Å r.m.s. deviation were used.

The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2009, 284, 26613-26619) copyright 2009.

Figures were selected by the author.