Functional model of subcomponent C1 of human complement

Weiss, Verena; Fauser, Charlotte; Engel, Jürgen

doi:10.1016/0022-2836(86)90325-6

Cited by 57 publications

(59 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Model (F) is consistent with the 'head-to-tail' structure proposed on the basis of chemical cross-linking [8]. Model (G) is consistent with electron micrographs of the protein obtained by Weiss et al [7,28]. Further studies are necessary in order to discriminate between the two alternative models.…”

Section: Modelssupporting

confidence: 83%

Neutron scattering study of the (γ‐B) catalytic domains of complement proteases Cl̄r and Cl̄s

et al. 1990

View full text Add to dashboard Cite

The catalytic domains of Cir and Cis, comprising the C-terminal region of the A chain (y), disulphide-linked to the B chain, were obtained by limited proteolysis of the native proteases with chymotrypsin and plasmin, respectively, and studied by small angle neutron scattering. For Cfs (y-B), a molar mass of 45 000 + 5000 g/mol, and a relatively large radius of gyration (Z&) of 28 f 1 A were determined, excluding a single globular domain. The corresponding values for Cir (y-B), (90,000 g/mol, R8 = 34 f 1 A) are consistent with a dimer involving the loose packing of two (y-B) subunits. Various models of the dimer are discussed in the light of neutron scattering and other data.

show abstract

Section: Modelssupporting

confidence: 83%

Neutron scattering study of the (γ‐B) catalytic domains of complement proteases Cl̄r and Cl̄s

et al. 1990

View full text Add to dashboard Cite

show abstract

“…2). That the C1r catalytic domain associates as a homodimer in solution has been demonstrated using various techniques (Villiers et al, 1985;Weiss et al, 1986;Lacroix et al, 2001). Likewise, the particular head-totail configuration seen in the structure is consistent with previous chemical cross-linking experiments and with the observation that deletion of the CCP 1 module prevents dimer formation (Lacroix et al, 1997(Lacroix et al, , 2001).…”

Section: From the Structure Of The C1r Catalytic Domain To A C1 Activsupporting

confidence: 86%

Deciphering complement mechanisms: The contributions of structural biology

Arlaud

Barlow

Gaboriaud

et al. 2007

Molecular Immunology

View full text Add to dashboard Cite

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.

show abstract

“…In this respect, the observation that the three residues involved in the coordination of Ca 2ϩ (Glu 45 , Asp 53 , and Asp 98 ), as well as Tyr 17 , which is closely associated to the Ca 2ϩ -binding site, are conserved in a large proportion of the CUB module repertoire (Fig. 3C), strongly supports the hypothesis that these residues define a particular CUB module subset with the specific ability to bind Ca 2ϩ .…”

Section: Characterization Of the C1s Interaction Domain-expressionmentioning

confidence: 56%

“…3B). In contrast, Tyr 17 and the Ca 2ϩ ligands Glu 45 , Asp 53 , and Asp 98 are conserved in approximately twothirds of the CUB module repertoire, strongly suggesting that these residues define a novel CUB module subset with the ability to bind Ca 2ϩ . This subset is possibly more representative in terms of structure than the spermadhesins.…”

Section: Characterization Of the C1s Interaction Domain-expressionmentioning

confidence: 99%

“…Furthermore, the current data (10,11,13) are consistent with the hypothesis that the CUB1-EGF moieties of C1r and C1s each contribute ligands for the interaction between the C1s-C1r-C1r-C1s tetramer and C1q sites located in the individual collagen-like stems of the protein (14,15). Based on these and other features, several low resolution models of the C1 complex have been proposed (2,16,17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

X-ray Structure of the Ca2+-binding Interaction Domain of C1s

Gregory

Thielens

Arlaud

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

C1, the complex that triggers the classical pathway of complement, is assembled from two modular proteases C1r and C1s and a recognition protein C1q. The N-terminal CUB1-EGF segments of C1r and C1s are key elements of the C1 architecture, because they mediate both Ca 2؉ -dependent C1r-C1s association and interaction with C1q. The crystal structure of the interaction domain of C1s has been solved and refined to 1.5 Å resolution. The structure reveals a head-to-tail homodimer involving interactions between the CUB1 module of one monomer and the epidermal growth factor (EGF) module of its counterpart. A Ca 2؉ ion is bound to each EGF module and stabilizes both the intra-and inter-monomer interfaces. Unexpectedly, a second Ca 2؉ ion is bound to the distal end of each CUB1 module, through six ligands contributed by Glu 45 , Asp 53 , Asp 98 , and two water molecules. These acidic residues and Tyr 17 are conserved in approximately two-thirds of the CUB repertoire and define a novel, Ca 2؉ -binding CUB module subset. The C1s structure was used to build a model of the C1r-C1s CUB1-EGF heterodimer, which in C1 connects C1r to C1s and mediates interaction with C1q. A structural model of the C1q/C1r/C1s interface is proposed, where the rod-like collagen triple helix of C1q is accommodated into a groove along the transversal axis of the C1r-C1s heterodimer.

show abstract

Functional model of subcomponent C1 of human complement

Cited by 57 publications

References 43 publications

Neutron scattering study of the (γ‐B) catalytic domains of complement proteases Cl̄r and Cl̄s

Neutron scattering study of the (γ‐B) catalytic domains of complement proteases Cl̄r and Cl̄s

Deciphering complement mechanisms: The contributions of structural biology

X-ray Structure of the Ca2+-binding Interaction Domain of C1s

Contact Info

Product

Resources

About