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Prolyl isomerization as a molecular memory in the allosteric regulation of the signal adapter protein c-CrkII.

Title data

Schmidpeter, Philipp A. M. ; Schmid, Franz X.:
Prolyl isomerization as a molecular memory in the allosteric regulation of the signal adapter protein c-CrkII.
In: The Journal of Biological Chemistry. Vol. 290 (30 January 2015) Issue 5 . - pp. 3021-3032.
ISSN 1083-351X
DOI: https://doi.org/10.1074/jbc.M114.617308

Abstract in another language

c-CrkII is a central signal adapter protein. A domain opening/closing reaction between its N- and C-terminal Src homology 3 domains (SH3N and SH3C, respectively) controls signal propagation from upstream tyrosine kinases to downstream targets. In chicken but not in human c-CrkII, opening/closing is coupled with cis/trans isomerization at Pro-238 in SH3C. Here, we used advanced double-mixing experiments and kinetic simulations to uncover dynamic domain interactions in c-CrkII and to elucidate how they are linked with cis/trans isomerization and how this regulates substrate binding to SH3N. Pro-238 trans → cis isomerization is not a simple on/off switch but converts chicken c-CrkII from a high affinity to a low affinity form. We present a double-box model that describes c-CrkII as an allosteric system consisting of an open, high affinity R state and a closed, low affinity T state. Coupling of the T-R transition with an intrinsically slow prolyl isomerization provides c-CrkII with a kinetic memory and possibly functions as a molecular attenuator during signal transduction.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 7735837
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 13:06
Last Modified: 22 Apr 2015 07:01
URI: https://eref.uni-bayreuth.de/id/eprint/10465