title: Recognition of the rotavirus mRNA 3' consensus by an asymmetric NSP3 homodimer.
abstract: Rotaviruses, the cause of life-threatening diarrhea in humans and cattle, utilize a functional homolog of poly(A) binding protein (PABP) known as nonstructural protein 3 (NSP3) for translation of viral mRNAs. NSP3 binds to viral mRNA 3' consensus sequences and circularizes the mRNA via interactions with eIF4G. The X-ray structure of the NSP3 RNA binding domain bound to a rotaviral mRNA 3' end has been determined. NSP3 is a novel, heart-shaped homodimer with a medial RNA binding cleft. The homodimer is asymmetric, and contains two similar N-terminal segments plus two structurally different C-terminal segments that intertwine to create a tunnel enveloping the mRNA 3' end. Biophysical studies demonstrate high affinity binding leading to increased thermal stability and slow dissociation kinetics, consistent with NSP3 function.
authors.affiliation: Laboratories of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Rahul C
authors.initials: RC
authors.lastname: Deo
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Groft
authors.forename: K R
authors.initials: KR
authors.lastname: Rajashankar
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Burley
mesh_terms: D000225:Adenine; D001665:Binding Sites / Q000235:genetics; D016384:Consensus Sequence; D003562:Cytidine; D019281:Dimerization; D006147:Guanine; D006801:Humans; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D012401:Rotavirus / Q000235:genetics*; D012400:Rotavirus Infections / Q000628:therapy; D017386:Sequence Homology, Amino Acid; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: C082740:NSP3 protein, Rotavirus; D012333:RNA, Messenger; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D003562:Cytidine; D006147:Guanine; D000225:Adenine