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Molecular determinants of a regulatory prolyl isomerization in the signal adapter protein c-CrkII

Title data

Schmidpeter, Philipp A. M. ; Schmid, Franz X.:
Molecular determinants of a regulatory prolyl isomerization in the signal adapter protein c-CrkII.
In: ACS Chemical Biology. Vol. 9 (16 May 2014) Issue 5 . - pp. 1145-1152.
ISSN 1554-8937
DOI: https://doi.org/10.1021/cb500001n

Abstract in another language

The cellular CT10 regulator of kinase protein (c-CrkII) transmits signals from oncogenic tyrosine kinases to cellular targets. Nuclear magnetic resonance studies had suggested that in chicken c-CrkII a native state prolyl cis-trans isomerization is involved in signal propagation. Corresponding evidence for the closely related human c-CrkII was not obtained. Here we analyzed the kinetics of folding and substrate binding of the two homologues and found that cis-trans isomerization of Pro238 determines target binding in chicken but not in human c-CrkII. A reciprocal mutational analysis uncovered residues that determine the isomeric state at Pro238 and transmit it to the binding site for downstream target proteins. The transfer of these key residues to human c-CrkII established a regulatory proline switch in this protein, as well. We suggest that Pro238 isomerization extends the lifetime of the signaling-active state of c-CrkII and thereby functions as a long-term molecular storage device.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 24571054
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Professorship Biochemistry - Univ.-Prof. Dr. Franz Xaver Schmid
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Professorship Biochemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 21 Apr 2015 13:29
Last Modified: 22 Apr 2015 07:10
URI: https://eref.uni-bayreuth.de/id/eprint/10474