title: Vaccinia virus complement control protein is monomeric, and retains structural and functional integrity after exposure to adverse conditions.
abstract: Vaccinia virus complement control protein (VCP) possesses the ability to inhibit both classical and alternative pathways of complement activation, as well as bind to heparin or heparan sulfate proteoglycans, making it a unique multifunctional protein with therapeutic potential. Recently, the structure of the complete molecule of VCP was determined by X-ray crystallography. Two or three VCP molecules were packed within the unit cells of both crystal forms. Using gel filtration, VCP has now been shown to exist as a monomer in solution. To test the stability of this molecule, VCP was studied by nuclear magnetic resonance (NMR) over a range of temperatures and by differential scanning calorimetry (DSC). It was also subjected to adverse physical conditions, including, freeze-thawing, changes in pH, changes in temperature, and storage at room temperature. VCP melts fully reversibly, and it maintained its 3-D structure and the ability to inhibit serum-induced hemolysis of sheep red blood cells after exposure to many extreme conditions. The robustness of VCP may be rationalized in terms of its architecture.
authors.affiliation: Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Smith
authors.forename: Gunasekaran
authors.initials: G
authors.lastname: Krishnasamy
authors.forename: Krishna H M
authors.initials: KH
authors.lastname: Murthy
authors.forename: Alan
authors.initials: A
authors.lastname: Cooper
authors.forename: Krystyna
authors.initials: K
authors.lastname: Bromek
authors.forename: Paul N
authors.initials: PN
authors.lastname: Barlow
authors.forename: Girish J
authors.initials: GJ
authors.lastname: Kotwal
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D005615:Freezing; D006461:Hemolysis / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D012756:Sheep; D013816:Thermodynamics; D014616:Vaccinia virus / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus