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PDBsum entry 2wng
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Cell adhesion
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PDB id
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2wng
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References listed in PDB file
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Key reference
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Title
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Structure of signal-Regulatory protein alpha: a link to antigen receptor evolution.
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Authors
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D.Hatherley,
S.C.Graham,
K.Harlos,
D.I.Stuart,
A.N.Barclay.
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Ref.
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J Biol Chem, 2009,
284,
26613-26619.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
from an Open Access publication published by the ASBMB:
J Biol Chem
(2009,
284,
26613-26619)
copyright 2009.
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