The Structure of Bovine Complement Component 3 Reveals the Basis for Thioester Function

Fredslund, Folmer; Jenner, L.; Husted, Lise Bjerre; Nyborg, Jens; Andersen, Gregers Rom; Sottrup‐Jensen, Lars

doi:10.1016/j.jmb.2006.06.009

Cited by 73 publications

(72 citation statements)

References 44 publications

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“…Our structure of the C3d:I domain complex together with the structures of C3 (26,27), the C3d complexes with factor H (20, 28), and CR2 (21) demonstrate that a substantial fraction of the surface of the C3 TE domain is involved in intra-or intermolecular contacts in one of the multiple functional states of C3. Strikingly, surface residues on the TE domain interacting with other domains in native C3 are almost perfectly separated from those surface patches forming contacts with fH, CR3, and CR2 in their C3d complexes.…”

Section: Significancementioning

confidence: 76%

Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3

Bajic¹,

Yatime²,

Sim

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

188

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Complement receptors (CRs), expressed notably on myeloid and lymphoid cells, play an essential function in the elimination of complement-opsonized pathogens and apoptotic/necrotic cells. In addition, these receptors are crucial for the cross-talk between the innate and adaptive branches of the immune system. CR3 (also known as Mac-1, integrin α M β 2 , or CD11b/CD18) is expressed on all macrophages and recognizes iC3b on complement-opsonized objects, enabling their phagocytosis. We demonstrate that the C3d moiety of iC3b harbors the binding site for the CR3 αI domain, and our structure of the C3d:αI domain complex rationalizes the CR3 selectivity for iC3b. Based on extensive structural analysis, we suggest that the choice between a ligand glutamate or aspartate for coordination of a receptor metal ion-dependent adhesion site-bound metal ion is governed by the secondary structure of the ligand. Comparison of our structure to the CR2:C3d complex and the in vitro formation of a stable CR3:C3d: CR2 complex suggests a molecular mechanism for the hand-over of CR3-bound immune complexes from macrophages to CR2-presenting cells in lymph nodes.innate immunity | phagocytosis | integrin receptor | structural biology

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Section: Significancementioning

confidence: 76%

Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3

Bajic¹,

Yatime²,

Sim

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

188

View full text Add to dashboard Cite

show abstract

“…Notably, this contention is also supported by the charge distribution on human and bovine C3b. Overall, bovine C3b is mostly electropositive, whereas human C3b is mostly electronegative (45,46).…”

Section: Discussionmentioning

confidence: 98%

Species Selectivity in Poxviral Complement Regulators Is Dictated by the Charge Reversal in the Central Complement Control Protein Modules

Yadav

Pyaram

Ahmad

et al. 2012

The Journal of Immunology

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Variola and vaccinia viruses, the two most important members of the family Poxviridae, are known to encode homologs of the human complement regulators named smallpox inhibitor of complement enzymes (SPICE) and vaccinia virus complement control protein (VCP), respectively, to subvert the host complement system. Intriguingly, consistent with the host tropism of these viruses, SPICE has been shown to be more human complement-specific than VCP, and in this study we show that VCP is more bovine complement-specific than SPICE. Based on mutagenesis and mechanistic studies, we suggest that the major determinant for the switch in species selectivity of SPICE and VCP is the presence of oppositely charged residues in the central complement control modules, which help enhance their interaction with factor I and C3b, the proteolytically cleaved form of C3. Thus, our results provide a molecular basis for the species selectivity in poxviral complement regulators.

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“…These data on intact C3, together with the previously available structure of a C3d construct produced in E. coli (Nagar et al, 1998), afforded insights into the molecular mechanisms of thioester protection and activation, which are essential for the covalent attachment of C3b to its target surfaces. These structural findings for human C3 were confirmed by the subsequent report of the structure of bovine C3 by Fredslund et al (2006). Recently, these structures were complemented by the structures of the activated C3b molecule (Janssen et al, 2006) and of C3b in complex with the cell-surface receptor and inhibitor, CRIg (Wiesmann et al, 2006).…”

Section: Crystal Structures Of C3 and Its Fragmentsmentioning

confidence: 62%

“…The crystal structures of C3 (Janssen et al, 2005;Fredslund et al, 2006) revealed that the two separate ␤ (res. 1-645) and ␣ (res.…”

Section: Domain Organization Of C3mentioning

confidence: 99%

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Deciphering complement mechanisms: The contributions of structural biology

Arlaud

Barlow

Gaboriaud

et al. 2007

Molecular Immunology

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Since the resolution of the first three-dimensional structure of a complement component in 1980, considerable efforts have been put into the investigation of this system through structural biology techniques, resulting in about a hundred structures deposited in the Protein Data Bank by the beginning of 2007. By revealing its mechanisms at the atomic level, these approaches significantly improve our understanding of complement, opening the way to the rational design of specific inhibitors. This review is co-authored by some of the researchers currently involved in the structural biology of complement and its purpose is to illustrate, through representative examples, how X-ray crystallography and NMR techniques help us decipher the many sophisticated mechanisms that underlie complement functions.

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The Structure of Bovine Complement Component 3 Reveals the Basis for Thioester Function

Cited by 73 publications

References 44 publications

Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3

Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3

Species Selectivity in Poxviral Complement Regulators Is Dictated by the Charge Reversal in the Central Complement Control Protein Modules

Deciphering complement mechanisms: The contributions of structural biology

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