Structures of the pleiotropic translational regulator Hfq and an Hfq-RNA complex: a bacterial Sm-like protein.
In prokaryotes, Hfq regulates translation by modulating the structure of numerous RNA molecules by binding preferentially to A/U-rich sequences. To elucidate the mechanisms of target recognition and translation regulation by Hfq, we determined the crystal structures of the Staphylococcus aureus Hfq and an Hfq-RNA complex to 1.55 and 2.71 A resolution, respectively. The structures reveal that Hfq possesses the Sm-fold previously observed only in eukaryotes and archaea. However, unlike these heptameric Sm proteins, Hfq forms a homo-hexameric ring. The Hfq-RNA structure reveals that the single-stranded hepta-oligoribonucleotide binds in a circular conformation around a central basic cleft, whereby Tyr42 residues from adjacent subunits stack with six of the bases, and Gln8, outside the Sm motif, provides key protein-base contacts. Such binding suggests a mechanism for Hfq function.
Schumacher
Maria A
MA
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97201-3098, USA.
Pearson
Robert F
RF
Møller
Thorleif
T
Valentin-Hansen
Poul
P
Brennan
Richard G
RG
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D015964:Gene Expression Regulation, Bacterial; D035001:Host Factor 1 Protein; D034982:Integration Host Factors; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000737:chemistry*; D013379:Substrate Specificity
D002352:Carrier Proteins; D035001:Host Factor 1 Protein; D034982:Integration Host Factors; D046911:Macromolecular Substances; D012329:RNA, Bacterial; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins