Combined mechanism of conformational selection and induced fit in U1A-RNA molecular recognition

Ikuo Kurisaki, Masayoshi Takayanagi, Masataka Nagaoka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

In this study, we demonstrate that U1A-RNA molecular recognition is mediated by a combined mechanism of conformational selection and induced fit. The binding of U1A to RNA has been discussed in the context of induced fit that involves the reorientation of the α-helix in the C-terminal region (Helix-C) of U1A to permit RNA access only when U1A correctly recognizes RNA. However, according to our molecular dynamics simulations, even in the absence of RNA, Helix-C spontaneously reoriented to permit RNA access. Nonetheless, such a conformational change was still incomplete. Helix-C was often partially or even fully unfolded and in an infrequent RNA-accessible conformation, which can be detected using state-of-the-art nuclear magnetic resonance methodology. These results suggest that the formation of an energetically stabilized complex is promoted by specific interactions between U1A and RNA. In conclusion, in the recognition of RNA by U1A protein, we propose a combined mechanism that requires the reorientation of Helix-C and the subsequent contact with RNA through conformational selection, although the stabilization of the U1A-RNA complex is caused by induced fit. We further propose a modification to the conventional assumption regarding the mechanism of U1A-RNA molecular recognition.

Original languageEnglish
Pages (from-to)3646-3657
Number of pages12
JournalBiochemistry
Volume53
Issue number22
DOIs
Publication statusPublished - 2014 Jun 10
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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