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. 1999 Oct 26;96(22):12379-83.
doi: 10.1073/pnas.96.22.12379.

Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus

A Carfí  1 , C A Smith, P J Smolak, J McGrew, D C Wiley
Affiliations

Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus

A Carfí et al. Proc Natl Acad Sci U S A. .

Abstract

Most poxviruses, including variola, the causative agent of smallpox, express a secreted protein of 35 kDa, vCCI, which binds CC-chemokines with high affinity. This viral protein competes with the host cellular CC-chemokine receptors (CCRs), reducing inflammation and interfering with the host immune response. Such proteins or derivatives may have therapeutic uses as anti-inflammatory agents. We have determined the crystal structure to 1.85-A resolution of vCCI from cowpox virus, the prototype of this poxvirus virulence factor. The molecule is a beta-sandwich of topology not previously described. A patch of conserved residues on the exposed face of a beta-sheet that is strongly negatively charged might have a role in binding of CC-chemokines, which are positively charged.

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Figures

Figure 1
Figure 1
Structure of cowpox vCCI: Ribbon diagrams. A and B are related by 90° rotation. Green arrows represent β-strands, blue ribbons, α helices. This figure was created with ribbons (30).
Figure 2
Figure 2
Secondary structure elements of the cowpox virus vCCI: Topology diagram.
Figure 3
Figure 3
Sequence alignment of six members of the poxvirus vCCI family (CPV, cowpox (31); RPV, rabbitpox virus (32); VV, vaccinia virus (33); VAV, variola virus (34); MV, myxomavirus (35); SFV, Shope fibromavirus). Strictly conserved residues (yellow) and the eight cysteines (green) are highlighted. The cysteines involved in disulfide bridges (*, #, @, &) and the exposed conserved residues (s) are also indicated. This figure was generated with Canvas 5.0.3 (Deneba Systems, Miami).
Figure 4
Figure 4
Ribbon diagram of the dimer formed by the NCS-related molecules in the crystal. This figure was created with ribbons (30).
Figure 5
Figure 5
Surface representation of vCCI. (A–C) Electrostatic potential of vCCI. A and B are in the same orientations as in Fig. 1 A and B, respectively, and C is the exposed face of β-sheet II (the molecule is rotated 180° compared with Fig. 5A). (D–F) Exposed conserved residues viewed as in A–C. This figure was generated with grasp (36).
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