title: Domain-swapped structure of the potent antiviral protein griffithsin and its mode of carbohydrate binding.
abstract: The crystal structure of griffithsin, an antiviral lectin from the red alga Griffithsia sp., was solved and refined at 1.3 A resolution for the free protein and 0.94 A for a complex with mannose. Griffithsin molecules form a domain-swapped dimer, in which two beta strands of one molecule complete a beta prism consisting of three four-stranded sheets, with an approximate 3-fold axis, of another molecule. The structure of each monomer bears close resemblance to jacalin-related lectins, but its dimeric structure is unique. The structures of complexes of griffithsin with mannose and N-acetylglucosamine defined the locations of three almost identical carbohydrate binding sites on each monomer. We have also shown that griffithsin is a potent inhibitor of the coronavirus responsible for severe acute respiratory syndrome (SARS). Antiviral potency of griffithsin is likely due to the presence of multiple, similar sugar binding sites that provide redundant attachment points for complex carbohydrate molecules present on viral envelopes.
authors.affiliation: Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, NCI-Frederick, Frederick, MD 21702, USA.
authors.forename: Natasza E
authors.initials: NE
authors.lastname: Ziółkowska
authors.forename: Barry R
authors.initials: BR
authors.lastname: O'Keefe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mori
authors.forename: Charles
authors.initials: C
authors.lastname: Zhu
authors.forename: Barbara
authors.initials: B
authors.lastname: Giomarelli
authors.forename: Fakhrieh
authors.initials: F
authors.lastname: Vojdani
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Palmer
authors.forename: James B
authors.initials: JB
authors.lastname: McMahon
authors.forename: Alexander
authors.initials: A
authors.lastname: Wlodawer
mesh_terms: D020418:Algal Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D019281:Dimerization; D037102:Lectins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D008969:Molecular Sequence Data; D037121:Plant Lectins; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects*
chemical_list: D020418:Algal Proteins; D000998:Antiviral Agents; D002241:Carbohydrates; D037102:Lectins; D037121:Plant Lectins; C499654:griffithsin protein, Griffithsia