PDBsum entry 1vve

Complement inhibitor

PDB id: 1vve

Contents

Protein chain

118 a.a. *

* Residue conservation analysis

PDB id:

1vve

Name:

Complement inhibitor

Title:

C-terminal half of vaccinia virus complement control protein, nmr, 21 structures

Structure:

Vaccinia virus complement control protein. Chain: a. Fragment: modules 3 and 4. Synonym: sp35, vcp, vaccinia virus sp35. Engineered: yes

Source:

Vaccinia virus. Organism_taxid: 10245. Gene: c21l. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Expression_system_variant: his4.

NMR struc:

21 models

Authors:

A.Wiles,I.D.Campbell,P.N.Barlow

Key ref:

A.P.Wiles et al. (1997). NMR studies of a viral protein that mimics the regulators of complement activation. J Mol Biol, 272, 253-265. PubMed id: 9299352 DOI: 10.1006/jmbi.1997.1241

Date:

25-Jun-97 Release date: 03-Dec-97

Protein chain

P68638  (VCP_VACCW) -  Complement control protein C3 from Vaccinia virus (strain Western Reserve)

Seq: 263 a.a.

Struc: 118 a.a.

DOI no: 10.1006/jmbi.1997.1241

J Mol Biol 272:253-265 (1997)

PubMed id: 9299352

NMR studies of a viral protein that mimics the regulators of complement activation.

A.P.Wiles, G.Shaw, J.Bright, A.Perczel, I.D.Campbell, P.N.Barlow.

ABSTRACT

Vaccinia virus complement control protein (VCP) is a 243-residue protein that is similar in sequence to the regulators of complement activation; its role is to defend the virus against attack by the host complement system. A fragment of this protein spanning the two complement protein (CP)-modules (residues 126 to 243) which make up the C-terminal half of VCP has been expressed in Pichia pastoris. A 15N-labelled sample was purified for the purposes of structure determination and measurements of dynamics in solution using NMR. Structures were calculated on the basis of 1767 NMR-derived distance and angle restraints, with a longer than normal high-temperature simulated annealing (SA) protocol which improved convergence. The viral CP-modules are structurally very similar to the 15th and 16th CP-modules of human factor H (fH; average r.m.s.d., for invariant Trp and Cys, four pair-wise comparisons,=1.2 A) but less similar to the fifth CP-module of fH (average r.m.s.d.=2.2 A). In the VCP fragment, the orientation of one module with respect to the other is clearly defined by the experimental data, and T1 measurements are consistent with only limited flexibility at the module-module interface. The r.m.s.d. over all of the 118 residues (backbone atoms) is 0.73 A. The intermodular orientation is better defined than, and significantly different from, that observed in a CP-module pair from fH (re-calculated using the extended SA protocol). In VCP the long axis of the second module is tilted by 59(+/-4) degrees with respect to the first module (50(+/-13) degrees in the fH pair), and twisted with respect to the first module by 22(+/-6) degrees (223(+/-17) degrees in fH). The differences between the human and viral proteins may be rationalised in terms of the lack of hydrogen-bond stabilised secondary structure in the N-terminal portion of fH module 16, and the number and type of amino acid side-chains which make up the interface. A similar intermodular interface may be predicted between the third and fourth module of human C4 binding protein and, probably, between the third and fourth modules of the guinea pig acrosomal matrix protein 67; but the formulation of general rules for predicting the structure of interfaces between CP-modules awaits further experimental data.

Selected figure(s)

Figure 7.
Figure 7. Topological similarity amongst members of the CP-module family. An overlay of all five CP-mod- ules for which detailed tertiary structures are now avail- able (all overlaid on fH15 using the alpha and beta carbon atoms of the invariant Trp and Cys residues). The backbones are shown as ribbons. The left-hand dia- gram emphasises the backbone (thick ribbon); the right- hand diagram shows the overlay of invariant Trp and Cys residues (stick representation). Key: red, H5; magenta, H15; yellow, H16; cyan, VCP3; white, VCP4.

Figure 8.
Figure 8. A comparison of human and viral proteins. A MOLSCRIPT (Kraulis, 1991) representation of the two CP-module pairs for which three-dimensional structures are now available. Refined and minimised average structures are shown. The tryptophan residues are shown as a CPK surface.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 272, 253-265) copyright 1997.

Figures were selected by an automated process.