Conformational ensemble of TteAdoCbl riboswitch provides stable structural elements for conformation selection and population shift in cobalamin recognition

Buyong Ma*, Ganggang Bai, Ruth Nussinov, Jienyu Ding, Yun Xing Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Cobalamin riboswitch is a cis-regulatory element widely found in the 5′-UTRs of the vitamin B12-associated genes in bacteria, resulting in modulation and production of a particular protein. Thermoanaerobacter tengcongensis (Tte) AdoCbl riboswitches are the largest of the known riboswitches with 210 nucleotides, partially due to its long peripheral P6-extension, which enable high affinity of AdoCbl. Two structural elements, T-loop/T-looplike motif and kissing loop are key to the global folding of the RNA. While the structure of the TteAdoCbl riboswitch complex is known, we still do not understand the structure and conformation before AdoCbl ligand recognition. In order to delineate the conformational changes and the stabilities of long-range interactions, we have performed extensive all-atom replica-exchange molecular dynamics simulations of the TteAdoCbl riboswitch with a total simulation time of 2296 ns. We found that both the T-loop/T-looplike motif and kissing loop are very stable with ligand binding. The gating conformation changes of P6-extension allow the ligand to bind to the preorganized kissing loop binding pocket. The T-loop/T-looplike motif has much more hydrogen bonds than observed in TteAdoCbl riboswitch complex crystal structure, indicating an allosteric response of the T-loop/T-looplike motif. Our study demonstrated that the conformational ensemble of TteAdoCbl riboswitch provides stable structural elements for conformation selection and population shift in cobalamin recognition.

Original languageEnglish
Pages (from-to)2589-2596
Number of pages8
JournalJournal of Physical Chemistry B
Volume125
Issue number10
DOIs
StatePublished - 18 Mar 2021

Funding

FundersFunder number
National Institutes of HealthHHSN261200800001E
National Cancer InstituteZIABC010379
Shanghai Jiao Tong University

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