PDBsum entry 1e5g

Complement inhibitor

PDB id: 1e5g

Contents

Protein chain

120 a.a. *

* Residue conservation analysis

PDB id:

1e5g

Name:

Complement inhibitor

Title:

Solution structure of central cp module pair of a pox virus complement inhibitor

Structure:

Complement control protein c3. Chain: a. Fragment: modules 2 and 3 residues 84-203. Synonym: sp35,28 kda protein, secretory protein 35, protein c3, vcp. Engineered: yes

Source:

Vaccinia virus. Organism_taxid: 10249. Strain: copenhagen. Gene: c21l. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

NMR struc:

50 models

Authors:

C.E.Henderson,K.Bromek,N.P.Mullin,B.O.Smith,D.Uhrin,P.N.Barlow

Key ref:

C.E.Henderson et al. (2001). Solution structure and dynamics of the central CCP module pair of a poxvirus complement control protein. J Mol Biol, 307, 323-339. PubMed id: 11243823 DOI: 10.1006/jmbi.2000.4477

Date:

25-Jul-00 Release date: 31-Aug-00

Protein chain

P68639  (VCP_VACCC) -  Complement control protein C3 from Vaccinia virus (strain Copenhagen)

Seq: 263 a.a.

Struc: 120 a.a.

DOI no: 10.1006/jmbi.2000.4477

J Mol Biol 307:323-339 (2001)

PubMed id: 11243823

Solution structure and dynamics of the central CCP module pair of a poxvirus complement control protein.

C.E.Henderson, K.Bromek, N.P.Mullin, B.O.Smith, D.Uhrín, P.N.Barlow.

ABSTRACT

The complement control protein (CCP) module (also known as SCR, CCP or sushi domain) is prevalent amongst proteins that regulate complement activation. Functional and mutagenesis studies have shown that in most cases two or more neighbouring CCP modules form specific binding sites for other molecules. Hence the orientation in space of a CCP module with respect to its neighbours and the flexibility of the intermodular junction are likely to be critical for function. Vaccinia virus complement control protein (VCP) is a complement regulatory protein composed of four tandemly arranged CCP modules. The solution structure of the carboxy-terminal half of this protein (CCP modules 3 and 4) has been solved previously. The structure of the central portion (modules 2 and 3, VCP approximately 2,3) has now also been solved using NMR spectroscopy at 37 degrees C. In addition, the backbone dynamics of VCP approximately 2,3 have been characterised by analysis of its (15)N relaxation parameters. Module 2 has a typical CCP module structure while module 3 in the context of VCP approximately 2,3 has some modest but significant differences in structure and dynamics to module 3 within the 3,4 pair. Modules 2 and 3 do not share an extensive interface, unlike modules 3 and 4. Only two possible NOEs were identified between the bodies of the modules, but a total of 40 NOEs between the short intermodular linker of VCP approximately 2,3 and the bodies of the two modules determines a preferred, elongated, orientation of the two modules in the calculated structures. The anisotropy of rotational diffusion has been characterised from (15)N relaxation data, and this indicates that the time-averaged structure is more compact than suggested by (1)H-(1)H NOEs. The data are consistent with the presence of many intermodular orientations, some of which are kinked, undergoing interconversion on a 10(-8)-10(-6) second time-scale. A reconstructed representation of modules 2-4 allows visualisation of the spatial arrangement of the 11 substitutions that occur in the more potent complement inhibitor from Variola (small pox) virus.

Selected figure(s)

Figure 3.
Figure 3. The solution structure of VCP vert, similar 2,3. Overlay of 50 calculated structures shown as backbone traces, superimposed (C^as) on (a) both modules; (b) module 2. (c) A Molscript [Kraulis 1991] representation of VCP vert, similar 2,3 in the same orientation as in (b).

Figure 6.
Figure 6. Superposition of VCP vert, similar 2,3 and VCP vert, similar 3,4 [Wiles et al 1997] using module 3. (a) A randomly selected sample of 25 structures from each of the VCP vert, similar 2,3 (cyan) and VCP vert, similar 3,4 (dark blue) sets of NMR structures. All structures are superimposed on the backbone of module 3 of the structure of VCP vert, similar 2,3 most similar to the average structure. Backbone atoms are shown. (b) A surface representation of VCP vert, similar 2,3 (module 2, cyan; module 3, light blue) and module 4 (dark blue) of VCP vert, similar 3,4. The orientation of all modules is the same as in 6(a). The side-chains of 11 residues that are replaced in the sequence of SPICE are coloured red, and labelled (and SPICE replacements shown in parantheses). VCP vert, similar 2,3 numbering is used except for substitutions in module 4 (italics) where VCP vert, similar 3,4 numbering is used.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 307, 323-339) copyright 2001.

Figures were selected by an automated process.