An RNA-binding chameleon.
The arginine-rich RNA binding motif is found in a wide variety of proteins, including several viral regulatory proteins. Although related at the primary sequence level, arginine-rich domains from different proteins adopt different conformations depending on the RNA site recognized, and in some cases fold only in the context of RNA. Here we show that the RNA binding domain of the Jembrana disease virus (JDV) Tat protein is able to recognize two different TAR RNA sites, from human and bovine immunodeficiency viruses (HIV and BIV, respectively), adopting different conformations in the two RNA contexts and using different amino acids for recognition. In addition to the conformational differences, the JDV domain requires the cyclin T1 protein for high-affinity binding to HIV TAR, but not to BIV TAR. The "chameleon-like" behavior of the JDV Tat RNA binding domain reinforces the concept that RNA molecules can provide structural scaffolds for protein folding, and suggests mechanisms for evolving distinct RNA binding specificities from a single multifunctional domain.
Smith
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Department of Biochemistry, University of California UCSF, San Francisco, CA 94143, USA.
Calabro
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Frankel
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D020816:Amino Acid Motifs; D001483:Base Sequence; D001665:Binding Sites; D024202:Electrophoretic Mobility Shift Assay; D019143:Evolution, Molecular; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D016087:Immunodeficiency Virus, Bovine / Q000235:genetics; D016086:Lentivirus / Q000737:chemistry* / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity; D013816:Thermodynamics; D015533:Transcriptional Activation
D015696:Gene Products, tat; D012367:RNA, Viral; C039919:RNA, recombinant; D016601:RNA-Binding Proteins; D012313:RNA