Optimizing the fold stability of the circularly permuted Trp-cage motif.

Abstract:

:Through optimization of the linker region and key stabilizing mutations, it has been possible to improve the stability of the circularly permuted (cp) Trp-cage miniprotein. However, even the most stable Trp-cage circular permutants are still less stable than the analogous standard topology (std) Trp-cages. Extending mutational studies of Trp-cage fold stability to cp-species, including analogs lacking chain terminal charges, has uncovered and quantitated some additional stabilizing and destabilizing interactions. Upon protonation, the circular permutants are destabilized to a much greater extent than the standard topology series. End effects, particularly Coulombic interactions, appear to be more important for the cp-series while the Y10/P4 interaction in the cp-series is not as significant a stabilizing feature as the corresponding Y3/P19 in the standard topology series.

journal_name

Biopolymers

journal_title

Biopolymers

authors

Graham KA,Byrne A,Mason M,Andersen NH

doi

10.1002/bip.23327

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

e23327

issue

12

eissn

0006-3525

issn

1097-0282

journal_volume

110

pub_type

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