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Visualizing spatially correlated dynamics that directs RNA conformational transitions.

Visualizing spatially correlated dynamics that directs RNA conformational transitions. Research Abstract Details 

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  • Visualizing spatially correlated dynamics that directs RNA conformational transitions. Abstract Text:

    qi zhangQi Zhang,andrew c stelzerAndrew C Stelzer,charles k fisherCharles K Fisher,hashim m al-hashimiHashim M Al-Hashimi,qi zhangQi Zhang,andrew c stelzerAndrew C Stelzer,charles k fisherCharles K Fisher,hashim m al-hashimiHashim M Al-Hashimi,qi zhangQi Zhang,andrew c stelzerAndrew C Stelzer,charles k fisherCharles K Fisher,hashim m al-hashimiHashim M Al-Hashimi,

    RNAs fold into three-dimensional (3D) structures that subsequently undergo large, functionally important, conformational transitions in response to a variety of cellular signals. RNA structures are believed to encode spatially tuned flexibility that can direct transitions along specific conformational pathways. However, this hypothesis has proved difficult to examine directly because atomic movements in complex biomolecules cannot be visualized in 3D by using current experimental methods. Here we report the successful implementation of a strategy using NMR that has allowed us to visualize, with complete 3D rotational sensitivity, the dynamics between two RNA helices that are linked by a functionally important trinucleotide bulge over timescales extending up to milliseconds. The key to our approach is to anchor NMR frames of reference onto each helix and thereby directly measure their dynamics, one relative to the other, using 'relativistic' sets of residual dipolar couplings (RDCs). Using this approach, we uncovered super-large amplitude helix motions that trace out a surprisingly structured and spatially correlated 3D dynamic trajectory. The two helices twist around their individual axes by approximately 53 degrees and 110 degrees in a highly correlated manner (R = 0.97) while simultaneously (R = 0.81-0.92) bending by about 94 degrees . Remarkably, the 3D dynamic trajectory is dotted at various positions by seven distinct ligand-bound conformations of the RNA. Thus even partly unstructured RNAs can undergo structured dynamics that directs ligand-induced transitions along specific predefined conformational pathways.

    Visualizing spatially correlated dynamics that directs RNA conformational transitions. Publishing Authors By Initials

    q zhangQ Zhang,ac stelzerAC Stelzer,ck fisherCK Fisher,hm al-hashimiHM Al-Hashimi,q zhangQ Zhang,ac stelzerAC Stelzer,ck fisherCK Fisher,hm al-hashimiHM Al-Hashimi,q zhangQ Zhang,ac stelzerAC Stelzer,ck fisherCK Fisher,hm al-hashimiHM Al-Hashimi,

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    Visualizing spatially correlated dynamics that directs RNA conformational transitions. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Nature

    VOLUME: 450

    Page Numbers: 1263-7

    Journal Abbreviation: Nature

    ISSN: 1476-4687

    DAY: 20

    MONTH: Dec

    YEAR: 2007

    Visualizing spatially correlated dynamics that directs RNA conformational transitions. Information

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    LANGUAGE: eng

    NlmUniqueID: 410462

    Visualizing spatially correlated dynamics that directs RNA conformational transitions. Keywords Mesh Terms:

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    Grant and Affiliation Information for Visualizing spatially correlated dynamics that directs RNA conformational transitions.

    AFFILIATION: Department of Chemistry and Biophysics, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.

    Country: England

    England Research PublicationEngland Research Publication

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    MEDLINETA: Nature

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