Structural Insight into the Specific Interaction between Murine SHPS-1/SIRPα and Its Ligand CD47

Nakaishi, A.; Hirose, Mayumi; Yoshimura, Masato; Oneyama, Chitose; Saito, Kimiko; Kuki, Nobuharu; Matsuda, M.; Honma, Nakayuki; Ohnishi, Hiroshi; Matozaki, Takashi; Okada, Masato; Nakagawa, Atsushi

doi:10.1016/j.jmb.2007.10.085

Cited by 23 publications

(36 citation statements)

References 51 publications

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“…As expected from the sequence similarity of the SIRPα and SIRPβ there is little difference in the overall structures of the domains but subtle differences in the loops were found with evidence for considerable mobility in these [17]. Sequence analysis and mutagenesis have failed to provide a simple explanation for the failure of SIRPβ to bind to CD47 [14,15,[17][18][19] but the structures suggest that this failure is due to subtle differences in the loops and involving indirect changes and not solely contact residues [17].…”

Section: The Structure Of Sirpα and Its Ligand Cd47mentioning

confidence: 88%

“…X-ray crystallography structures have been determined for the ligand binding domain of mouse, rat and human SIRPα [14][15][16], the single IgSF domain of CD47, a complex of SIRPα domain 1 and CD47, the N terminal domains of two alleles of SIRPβ (the activating receptor) and SIRPγ [16] and a NMR structure for SIRPβ (Protein Data Bank Code; 2D9C). The interacting domains are typical IgSF V-set domains but the binding site of SIRPα is highly convoluted and made up from loops at the end of the domain in a manner analogous to binding of antigens by immunoglobulins and the T cell receptor rather than involving the faces of the domain as in most cell cell interaction proteins (see [17]).…”

Section: The Structure Of Sirpα and Its Ligand Cd47mentioning

confidence: 99%

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Signal regulatory protein alpha (SIRPα)/CD47 interaction and function

Barclay

2009

Current Opinion in Immunology

101

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SummarySIRPα is an inhibitory receptor present on myeloid cells that interacts with a widely distributed membrane protein CD47. The activating member SIRPβ, despite extensive sequence similarity to SIRPα in the extracellular region, shows negligible binding to CD47. The SIRPα / CD47 interaction is unusual in that it can lead to bidirectional signalling through both SIRPα and CD47. This review concentrates on the interactions of SIRPα with CD47 where recent data have shed light on the structure of the proteins including determining why the activating SIRPβ does not bind CD47, evidence of extensive polymorphisms and implication for the evolution and function of this protein and paired receptors in general. The interaction may be modified by endocytosis of the receptors, cleavage by proteolysis and through interactions of surfactant proteins.

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Section: The Structure Of Sirpα and Its Ligand Cd47mentioning

confidence: 88%

Section: The Structure Of Sirpα and Its Ligand Cd47mentioning

confidence: 99%

Signal regulatory protein alpha (SIRPα)/CD47 interaction and function

Barclay

2009

Current Opinion in Immunology

101

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“…Interpretation of the recently solved crystal structures of soluble SIRP␣D1 suggested the formation of transdimers (26,27,29). However, subsequent analyses failed to demonstrate dimerization of soluble SIRP␣D1 under native conditions (27).…”

Section: Sirp␣ Forms Noncovalently Linkedmentioning

confidence: 99%

“…However, subsequent analyses failed to demonstrate dimerization of soluble SIRP␣D1 under native conditions (27). Given our evidence that the full-length ectodomain of SIRP␣ may dimerize, we tested whether SIRP␣D1 also dimerizes under similar conditions.…”

Section: Sirp␣ Forms Noncovalently Linkedmentioning

confidence: 99%

“…However, little is known about the contributions of the membrane-proximal immunoglobulin domains of SIRP␣. Previously published analyses of protein sequences indicated that proximal domains contained IgC motifs and are highly homologous among members of the SIRP family (6,(27)(28)(29)(30). Given that many known IgC domains associate with other IgC domains, others have speculated that SIRP␣ may form dimers and higher order structures.…”

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confidence: 99%

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The Role of cis Dimerization of Signal Regulatory Protein α (SIRPα) in Binding to CD47

Lee

Weber

Laur

et al. 2010

Journal of Biological Chemistry

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Interaction of SIRP␣ with its ligand, CD47, regulates leukocyte functions, including transmigration, phagocytosis, oxidative burst, and cytokine secretion. Recent progress has provided significant insights into the structural details of the distal IgV domain (D1) of SIRP␣. However, the structural roles of proximal IgC domains (D2 and D3) have been largely unstudied. The high degree of conservation of D2 and D3 among members of the SIRP family as well as the propensity of known IgC domains to assemble in cis has led others to hypothesize that SIRP␣ forms higher order structures on the cell surface. Here we report that SIRP␣ forms noncovalently linked cis homodimers. Treatment of SIRP␣-expressing cells with a membrane-impermeable cross-linker resulted in the formation of SDS-stable SIRP␣ dimers and oligomers. Biochemical analyses of soluble recombinant extracellular regions of SIRP␣, including domain truncation mutants, revealed that each of the three extracellular immunoglobulin loops of SIRP␣ formed dimers in solution. Coimmunoprecipitation experiments using cells transfected with different affinity-tagged SIRP␣ molecules revealed that SIRP␣ forms cis dimers. Interestingly, in cells treated with tunicamycin, SIRP␣ dimerization but not CD47 binding was inhibited, suggesting that a SIRP␣ dimer is probably bivalent. Last, we demonstrate robust dimerization of SIRPa in adherent, stimulated human neutrophils. Collectively, these data are consistent with SIRP␣ being expressed on the cell surface as a functional cis-linked dimer. Signal regulatory proteins (SIRPs)2 are immunoglobulin superfamily members and include SIRP␣, SIRP␤, and SIRP␥ (1, 2). Expression of SIRPs is largely restricted to leukocytes, where SIRP␣ and SIRP␤ are expressed in myeloid lineages, and SIRP␥ is expressed in lymphocytes (1, 2). Interestingly, SIRP␣ is also expressed in smooth muscle cells and neurons and has important signaling properties (3-5). The extracellular domains of SIRPs consist of a membrane-distal Ig variable-like (IgV) fold (D1), and two membrane-proximal Ig constant-like (IgC) folds (D2D3). The ectodomains of the various SIRP family members share a high degree of homology between their respective protein sequences. In contrast, the cytoplasmic signaling elements of different SIRPs differ greatly. For instance, the cytoplasmic tail of SIRP␣ contains four immunoreceptor tyrosine-based inhibitory motifs, which recruit Src homology 2 phosphatases upon phosphorylation (6). In contrast, SIRP␤ and SIRP␥ have short cytoplasmic tails that are only a few amino acids long. SIRP␤ associates with the immunoreceptor tyrosine-based activating motif containing adaptor protein DAP12 through charge interactions in the transmembrane regions (7,8). On the other hand, SIRP␥, lacking known signaling motifs, has been presumed to be a decoy receptor (9). However, a recent report suggests that SIRP␥ on T cells may be able to transmit signals that can regulate transendothelial migration (10). The major cellular ligand of SIRP␣ and SIRP␥ is CD47, a ubiquito...

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Grading the commercial optical biosensor literature—Class of 2008: ‘The Mighty Binders’

Rich

Myszka

2009

J of Molecular Recognition

141

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Optical biosensor technology continues to be the method of choice for label-free, real-time interaction analysis. But when it comes to improving the quality of the biosensor literature, education should be fundamental. Of the 1413 articles published in 2008, less than 30% would pass the requirements for high-school chemistry. To teach by example, we spotlight 10 papers that illustrate how to implement the technology properly. Then we grade every paper published in 2008 on a scale from A to F and outline what features make a biosensor article fabulous, middling or abysmal. To help improve the quality of published data, we focus on a few experimental, analysis and presentation mistakes that are alarmingly common. With the literature as a guide, we want to ensure that no user is left behind.

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Structural Insight into the Specific Interaction between Murine SHPS-1/SIRPα and Its Ligand CD47

Cited by 23 publications

References 51 publications

Signal regulatory protein alpha (SIRPα)/CD47 interaction and function

Signal regulatory protein alpha (SIRPα)/CD47 interaction and function

The Role of cis Dimerization of Signal Regulatory Protein α (SIRPα) in Binding to CD47

Grading the commercial optical biosensor literature—Class of 2008: ‘The Mighty Binders’

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