PDBsum entry 2jjs

Cell adhesion

PDB id: 2jjs

Contents

Protein chains

116 a.a. *

116 a.a. *

Ligands

NAG ×6

Metals

IOD ×18

Waters ×540

* Residue conservation analysis

PDB id:

2jjs

Name:

Cell adhesion

Title:

Structure of human cd47 in complex with human signal regulatory protein (sirp) alpha

Structure:

Tyrosine-protein phosphatase non-receptor type substrate 1. Chain: a, b. Fragment: n-terminal ectodomain, residues 31-148. Synonym: sirp alpha, shp substrate 1, shps-1, inhibitory receptor shps-1, signal regulatory protein alpha-1, sirp-alpha-1, sirp-alpha- 2, sirp-alpha- 3, myd-1 antigen, brain ig-like molecule with tyrosine- based activation motifs, bit, macrophage fusion receptor, p84, cd172a antigen. 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:

1.85Å R-factor: 0.171 R-free: 0.213

Authors:

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

Key ref:

D.Hatherley et al. (2008). Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47. Mol Cell, 31, 266-277. PubMed id: 18657508 DOI: 10.1016/j.molcel.2008.05.026

Date:

22-Apr-08 Release date: 05-Aug-08

Protein chains

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

Seq: 504 a.a.

Struc: 116 a.a.*

Protein chains

Q08722  (CD47_HUMAN) -  Leukocyte surface antigen CD47 from Homo sapiens

Seq: 323 a.a.

Struc: 116 a.a.*

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

DOI no: 10.1016/j.molcel.2008.05.026

Mol Cell 31:266-277 (2008)

PubMed id: 18657508

Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47.

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

ABSTRACT

CD47 is a widely distributed cell-surface protein that acts a marker of self through interactions of myeloid and neural cells. We describe the high-resolution X-ray crystallographic structures of the immunoglobulin superfamily domain of CD47 alone and in complex with the N-terminal ligand-binding domain of signal regulatory protein alpha (SIRPalpha). The unusual and convoluted interacting face of CD47, comprising the N terminus and loops at the end of the domain, intercalates with the corresponding regions in SIRPalpha. We have also determined structures of the N-terminal domains of SIRPbeta, SIRPbeta(2), and SIRPgamma; proteins that are closely related to SIRPalpha but bind CD47 with negligible or reduced affinity. These results explain the specificity of CD47 for the SIRP family of paired receptors in atomic detail. Analysis of SIRPalpha polymorphisms suggests that these, as well as the activating SIRPs, may have evolved to counteract pathogen binding to the inhibitory SIRPalpha receptor.

Selected figure(s)

Figure 2.
Figure 2. Crystal Structures of the IgSF Domain of CD47
(A) The secondary structure of CD47 is shown above the sequence of the IgSF domain of human CD47 with arrows and cylinders representing β sheets and α helices, respectively. The N-terminal glutamine residue that cyclizes to form a pyroglutamate is boxed. The cysteine residues that form a conserved disulphide bond between β sheets are highlighted in yellow. C15, which forms a disulphide link with the 5 transmembrane helix C-terminal domain of CD47, is starred. Residues where N-linked glycosylation was observed in at least one monomer of CD47 are colored magenta.
(B) CD47 (shown as ribbons) crystallized as a dimer where the G strands are swapped between pairs of molecules. The structure is color ramped from blue (N terminus) to red (C terminus), and the strands are labeled A–G. The three insets show the N-terminal pyroglutamate, the region between the domains together with the Mg^2+ that is assumed to facilitate the strand-swap, and one of the sites of N-linked glycosylation. In all insets, the final refined model is shown in 2F[O]-F[C] electron density (1.3 σ) calculated at the end of refinement.

Figure 3.
Figure 3. The Structure of CD47 in Complex with SIRPα
(A) The structure of CD47 (yellow ribbons) complexed with SIRPα d1 (blue ribbons). Sites of N-linked glycosylation are shown as magenta spheres. A schematic representation of the 5 transmembrane helix C-terminal domain of CD47 is shown, including the proposed disulfide bond between C15 (Gly in our structure; yellow sphere) and C245. The inset shows a close-up view of the CD47/SIRPα interaction interface.
(B) The structure of CD47 in complex with SIRPα (yellow) is almost indistinguishable from that of CD47 solved in isolation (orange and gray). Remarkably, the interaction of strand G with the rest of the CD47 monomer is almost identical regardless of whether it is strand swapped or not. The inset shows L101 and T102, which mediate the turn at the tip of the FG loop in the non-strand-swapped CD47 monomer.
(C) The surface of SIRPα as viewed by CD47. The molecular surface of SIRPα d1 is shown, colored by electrostatic potential. Regions of CD47 that interact with SIRPα are shown as sticks. In (C) and (D), areas of particular interest are identified by roman numerals (see [E]) and loop/strand names are shown, with NA denoting the N-terminal 6 residues of CD47.
(D) The surface of CD47 as viewed by SIRPα. The molecular surface of CD47 is shown, colored by electrostatic potential. Loops of SIRPα that interact with CD47 are shown as sticks.
(E) Selected portions of the interface. Residues of CD47 (yellow carbon atoms) and SIRPα (blue carbon atoms) are shown as sticks, and water molecules are shown as red spheres. The molecular surface of SIRPα is shown (white, semitransparent). Hydrogen bonds and salt bridges are shown as orange dashes. The roman numerals of the panels identify the regions of the interaction on the molecular surfaces in (C) and (D).

The above figures are reprinted by permission from Cell Press: Mol Cell (2008, 31, 266-277) copyright 2008.

Figures were selected by an automated process.