Thermostabilization mechanisms in thermophilic versus mesophilic three‐helix bundle proteins
In: Journal of Computational Chemistry, Jg. 43 (2021-11-05), S. 197-205
Online
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Zugriff:
The engineered three-helix bundle, UVF, is thermostabilized entropically due to heightened, native-state dynamics. However, it is unclear whether this thermostabilization strategy is observed in natural proteins from thermophiles. We performed all-atom, explicit solvent molecular dynamics simulations of two three-helix bundles from thermophilic H. butylicus (2lvsN and 2lvsC) and compared their dynamics to a mesophilic three-helix bundle, the Engrailed homeodomain (EnHD). Like UVF, 2lvsC had heightened native dynamics, which it maintained without unfolding at 100°C. Shortening and rigidification of loops in 2lvsN and 2lvsC and increased surface hydrogen bonds in 2lvsN were observed, as is common in thermophilic proteins. A buried disulfide and salt bridge in 2lvsN and 2lvsC, respectively, provided some stabilization, and addition of a homologous disulfide bond in EnHD slowed unfolding. The transferability and commonality of stabilization strategies among members of the three-helix bundle fold suggest that these strategies may be general and deployable in designing thermostable proteins.
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Thermostabilization mechanisms in thermophilic versus mesophilic three‐helix bundle proteins
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Autor/in / Beteiligte Person: | McCully, Michelle E. ; Yearwood, Lauren M. ; Nguyen, Catrina |
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Zeitschrift: | Journal of Computational Chemistry, Jg. 43 (2021-11-05), S. 197-205 |
Veröffentlichung: | Wiley, 2021 |
Medientyp: | unknown |
ISSN: | 1096-987X (print) ; 0192-8651 (print) |
DOI: | 10.1002/jcc.26782 |
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