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Folding of RNase T1 is decelerated by a specific tertiary contact in a folding intermediate

Titelangaben

Kiefhaber, Thomas ; Grunert, Hans Peter ; Hahn, Ulrich ; Schmid, Franz X.:
Folding of RNase T1 is decelerated by a specific tertiary contact in a folding intermediate.
In: Proteins. Bd. 12 (1992) Heft 2 . - S. 171-179.
ISSN 1097-0134
DOI: https://doi.org/10.1002/prot.340120210

Abstract

The replacement of tryptophan 59 of ribonuclease T1 by a tyrosine residue does not change the stability of the protein. However, it leads to a strong acceleration of a major, proline-limited reaction that is unusually slow in the refolding of the wild-type protein. The distribution of fast- and slow-folding species and the kinetic mechanism of slow folding are not changed by the mutation. Trp-59 is in close contact to Pro-39 in native RNase T1 and probably also in an intermediate that forms rapidly during folding. We suggest that this specific interaction interferes with the trans----cis reisomerization of the Tyr-38-Pro-39 bond at the stage of a native-like folding intermediate. The steric hindrance is abolished either by changing Trp-59 to a less bulky residue, such as tyrosine, or, by a destabilization of folding intermediates at increased concentrations of denaturant. Under such conditions folding of the wild-type protein and of the W59Y variant no longer differ. These results provide strong support for the proposal that trans----cis isomerization of Pro-39 is responsible for the major, very slow refolding reaction of RNase T1. They also indicate that specific tertiary interactions in folding intermediates do exist, but do not necessarily facilitate folding. They can have adverse effects and decelerate rate-limiting steps by trapping partially folded structures.

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Publikationsform: Artikel in einer Zeitschrift
Begutachteter Beitrag: Ja
Zusätzliche Informationen: PubMed-ID: 1603806
Institutionen der Universität: Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Ehemalige Professoren > Professur Biochemie - Univ.-Prof. Dr. Franz Xaver Schmid
Fakultäten
Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften
Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie
Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Professur Biochemie
Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Ehemalige Professoren
Titel an der UBT entstanden: Ja
Themengebiete aus DDC: 500 Naturwissenschaften und Mathematik > 540 Chemie
Eingestellt am: 13 Mai 2015 06:29
Letzte Änderung: 05 Sep 2022 11:49
URI: https://eref.uni-bayreuth.de/id/eprint/13440