Mosaic Cooperativity in Slow Polypeptide Topological Isomerization Revealed by Residue-Specific NMR Thermodynamic Analysis

Daisuke Fujinami, Hajime Motomura, Hiraku Oshima, Abdullah Al Mahin, Khaled M. Elsayed, Takeshi Zendo, Yuji Sugita, Kenji Sonomoto, Daisuke Kohda

Research output: Contribution to journalArticle

Abstract

Slow polypeptide conformational changes on time scales of >1 s are generally assumed to be highly cooperative two-state transitions, reflecting the high energy barrier. However, few experimental characterizations have tested the validity of this assumption. We performed residue-specific NMR thermodynamic analysis of the 27-residue lantibiotic peptide, nukacin ISK-1, to characterize the isomerization between two topological states on the second time scale. Unexpectedly, the thermal transition behaviors were distinct among peptide regions, indicating that the topological isomerization process is a mosaic of different degrees of cooperativity. The conformational change path between the two NMR structures was deduced by a targeted molecular dynamics simulation. The unique side-chain threading motions through the monosulfide rings are the structural basis of the high energy barrier, and the nonlocal interactions in the hydrophobic core are the structural basis of the cooperativity. Taken together, we provide an energetic description of the topological isomerization of nukacin ISK-1.

Original languageEnglish
Pages (from-to)1934-1939
Number of pages6
JournalJournal of Physical Chemistry Letters
Volume11
Issue number5
DOIs
Publication statusPublished - Mar 5 2020

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Physical and Theoretical Chemistry

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