title: An isostructural G-G to A-A substitution within the HIV RRE RNA switches the specificity towards arginine-rich peptides.
abstract: The HIV Rev protein utilizes a short alpha-helical arginine-rich RNA-binding domain to bind deeply within the major groove of an internal loop region of the Rev-response element (RRE) RNA. A G48-G71 base-pair which covaries to an isostructural A48-A71 base pair has been shown to play an important structure role in Rev-RRE binding. On the other hand, a high affinity RRE-binding peptide aptamer, the K1 peptide, was shown to have low binding affinity towards the RRE A48-A71 mutant, suggesting that the K1 peptide was recognizing the G48-G71 base-pair. In this study, in an attempt to understand the basis for the recognition of the G48-G71 base-pair by the K1 peptide, the selection of peptides that bind to the RRE A48A71 (RREAA) mutant was carried out. As a result, a peptide specific for the mutant, the LDN1 peptide, was identified. The LDN1 peptide was found to bind to the internal loop region of the RREAA, as in the case of the K1-RRE interaction. However, amino acids important for LDN1-binding to RREAA, were found to be distinct from those important for K1-binding to the RRE. These results demonstrate how subtle changes in RNA structure can dramatically alter the peptide-binding specificity of an RNA.
authors.affiliation: Department of Life Sciences, Tokyo Gakugei University, Koganei, Tokyo 184-8501, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Aoyama
authors.forename: Maki
authors.initials: M
authors.lastname: Sugaya
authors.forename: Chisato
authors.initials: C
authors.lastname: Kobayashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Masuda
authors.forename: Tae
authors.initials: T
authors.lastname: Maeda
authors.forename: Taiichi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Gota
authors.initials: G
authors.lastname: Kawai
authors.forename: Akira
authors.initials: A
authors.lastname: Katoh
authors.forename: Kazuo
authors.initials: K
authors.lastname: Harada
mesh_terms: D000225:Adenine / Q000737:chemistry; D001120:Arginine / Q000737:chemistry*; D020029:Base Pairing; D001665:Binding Sites; D006147:Guanine / Q000737:chemistry; D006678:HIV / Q000235:genetics*; D009154:Mutation; D010455:Peptides / Q000737:chemistry*; D020218:Response Elements; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D010455:Peptides; D054321:rev Gene Products, Human Immunodeficiency Virus; D006147:Guanine; D001120:Arginine; D000225:Adenine