title: A Siglec-like sialic-acid-binding motif revealed in an adenovirus capsid protein.
abstract: Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are a family of transmembrane receptors that are well documented to play roles in regulation of innate and adaptive immune responses. To see whether the features that define the molecular recognition of sialic acid were found in other sialic-acid-binding proteins, we analyzed 127 structures with bound sialic acids found in the Protein Data Bank database. Of these, the canine adenovirus 2-fiber knob protein showed close local structural relationship to Siglecs despite low sequence similarity. The fiber knob harbors a noncanonical sialic-acid recognition site, which was then explored for detailed specificity using a custom glycan microarray comprising 58 diverse sialosides. It was found that the adenoviral protein preferentially recognizes the epitope Neu5Acα2-3[6S]Galβ1-4GlcNAc, a structure previously identified as the preferred ligand for Siglec-8 in humans and Siglec-F in mice. Comparison of the Siglec and fiber knob sialic-acid-binding sites reveal conserved structural elements that are not clearly identifiable from the primary amino acid sequence, suggesting a Siglec-like sialic-acid-binding motif that comprises the consensus features of these proteins in complex with sialic acid.
authors.affiliation: Departments of Chemical Physiology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Rademacher
authors.forename: Thierry
authors.initials: T
authors.lastname: Bru
authors.forename: Ryan
authors.initials: R
authors.lastname: McBride
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Robison
authors.forename: Corwin M
authors.initials: CM
authors.lastname: Nycholat
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kremer
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
mesh_terms: D006516:Adenoviruses, Canine / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011134:Polysaccharides / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000235:genetics / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D036022:Capsid Proteins; D011134:Polysaccharides; D012333:RNA, Messenger; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D012794:Sialic Acids; C018315:hexon capsid protein, Adenovirus