Solution structure of the X4 protein coded by the SARS related coronavirus reveals an immunoglobulin like fold and suggests a binding activity to integrin I domains.
The SARS related Coronavirus genome contains a variety of novel accessory genes. One of these, called ORF7a or ORF8, code for a protein, known as 7a, U122 or X4. We set out to determine the three-dimensional structure of the soluble ectodomain of this type-I transmembrane protein by nuclear magnetic resonance spectroscopy. The fold of the protein is the first member of a further variation of the immunoglobulin like beta-sandwich fold. Because X4 does not reveal significant sequence homologies to proteins in the data bases, we carried out a structure based similarity search for proteins with known function. High structural similarity to Dl domains of ICAM-1 and ICAM-2, and common features in amino acid sequence between X4 and ICAM-1, suggest X4 to possess binding activity for the alpha(L) integrin I domain of LFA-1. Further, based on this structure based prediction, potential functions of X4 in virus replication and pathogenesis are discussed.
Hänel
Karen
K
Forschungszentrum Jülich, Institut für Biologische Informationsverarbeitung (IBI-2), Germany.
Stangler
Thomas
T
Stoldt
Matthias
M
Willbold
Dieter
D
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000737:chemistry; D003001:Cloning, Molecular; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D016023:Integrins / Q000737:chemistry*; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry; D007375:Interleukin-1 / Q000737:chemistry; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry*; D014763:Viral Matrix Proteins / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D007136:Immunoglobulins; D016023:Integrins; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C488151:sars7a protein, SARS virus; D018799:Intercellular Adhesion Molecule-1