at Google ScholarTitle 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
(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 > Professor 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: | 28 Feb 2023 13:59 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/10465 |