PDBsum entry 1g40

Immune system

PDB id: 1g40

Contents

Protein chains

243 a.a. *

* Residue conservation analysis

Obsolete entry

PDB id:

1g40

Name:

Immune system

Title:

Crystal structure of a complement protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans

Structure:

Complement control protein. Chain: a, b. Engineered: yes

Source:

Vaccinia virus. Organism_taxid: 10245. Expressed in: pichia pastoris. Expression_system_taxid: 4922

Resolution:

2.20Å R-factor: 0.198 R-free: 0.234

Authors:

K.H.M.Murthy,S.A.Smith,V.K.Ganesh,K.W.Judge,N.Mullin,P.N.Barlow, C.M.Ogata,G.K.Kotwal

Key ref:

K.H.Murthy et al. (2001). Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans. Cell, 104, 301-311. PubMed id: 11207370 DOI: 10.1016/S0092-8674(01)00214-8

Date:

25-Oct-00 Release date: 07-Feb-01

Protein chains

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

Seq: 263 a.a.

Struc: 243 a.a.

DOI no: 10.1016/S0092-8674(01)00214-8

Cell 104:301-311 (2001)

PubMed id: 11207370

Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans.

K.H.Murthy, S.A.Smith, V.K.Ganesh, K.W.Judge, N.Mullin, P.N.Barlow, C.M.Ogata, G.J.Kotwal.

ABSTRACT

Vaccinia virus complement control protein (VCP) inhibits both pathways of complement activation through binding the third and fourth components. A homolog of mammalian regulators of complement activation, its ability to bind heparin endows VCP with additional activities of significance to viral infectivity. The structure of VCP reveals a highly extended molecule with a putative heparin recognition site at its C-terminal end. A second cluster of positive charges provides a possibly overlapping binding site for both heparin and complement components. Experiments suggested by the structure indicate that VCP can bind heparin and control complement simultaneously. This, the structure of any intact regulator of complement activation, along with attendant functional insights, will stimulate the design of new therapeutic inhibitors of complement.

Selected figure(s)

Figure 1.
Figure 1. Five Independent Molecules Are Similar(a) Stereo pair of superposed Cα traces of all five crystallographically independent molecules in the two crystal forms are shown. Molecule A in form I crystals is colored red, molecule B, blue, and molecules C, D, and E in form II crystals are colored magenta, cyan, and yellow respectively. CCP domains are labeled mod1–mod4.(b) A Cα trace of molecule A from Form I crystals is shown in magenta in the same orientation as in (a). Every 10^th Cα has been colored yellow and numbered. The N- and C-terminal residues are shown in cyan and labeled.

Figure 5.
Figure 5. Stereo View of Interaction of VCP with HeparinA Cα trace of residues 213–242 of VCP is shown in orange. Carbohydrate is shown with carbons colored gray; oxygen, red; nitrogen, blue; and sulfur, yellow. Side chains of the four basic residues of acidic and basic FGF and VCP that were superimposed are shown in red, magenta, and cyan, respectively. VCP side chains are labeled. The figure was composed using a rigid body transformation of VCP main chain on to the basic FGF heparin binding segment. The side chains of the Lys residues in VCP have been rotated to point toward the heparin fragment. The side chain of Lys 214 is beyond hydrogen bonding distance from heparin as currently modeled. Main chain movements of 1–2 Å will be required to bring its side chain within interacting distance.

The above figures are reprinted by permission from Cell Press: Cell (2001, 104, 301-311) copyright 2001.

Figures were selected by an automated process.