All but the shortest polymorphic forms of the viral receptor DC-SIGNR assemble into stable homo- and heterotetramers.
Polymorphisms that affect the length of the extracellular neck region of the endothelial receptor DC-SIGNR (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related protein) have been linked to differences in susceptibility to infection by enveloped viruses. We have characterized the effects of these polymorphisms on the ability of DC-SIGNR to form tetramers containing the clusters of sugar-binding sites needed for binding to viral envelope glycoproteins. Chemical cross-linking and analytical ultracentrifugation experiments have been used to show that only the smallest form of DC-SIGNR is defective in homotetramer assembly. A novel affinity-tagging approach has been employed to demonstrate that, contrary to previous speculation, heterotetramers can be assembled efficiently from DC-SIGNR polypeptides of different lengths. The heterotetramers are stable and can be detected in fibroblasts transfected with multiple forms of DC-SIGNR. These results provide a molecular basis for interpreting the way polymorphisms affect interactions with viruses.
Guo
Yuan
Y
Division of Molecular Biosciences, Imperial College, London SW7 2AZ, United Kingdom.
Atkinson
Claire E
CE
Taylor
Maureen E
ME
Drickamer
Kurt
K
D000818:Animals; D019921:Biotinylation; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019281:Dimerization; D005347:Fibroblasts / Q000378:metabolism; D005690:Galactose / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D007700:Kinetics; D037181:Lectins, C-Type / Q000737:chemistry* / Q000502:physiology*; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000502:physiology*; D014162:Transfection
C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; D006023:Glycoproteins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D005690:Galactose