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| Content Provider | PubMed Central |
|---|---|
| Author | Wall, Michael E. Francis, Sharron H. Corbin, Jackie D. Grimes, Kennard Robyn, Richie-jannetta Kotera, Jun Macdonald, Brian A. Gibson, Rowena R. Trewhella, Jill |
| Copyright Year | 2003 |
| Abstract | Using small-angle x-ray scattering, we have observed the cGMP-induced elongation of an active, cGMP-dependent, monomeric deletion mutant of cGMP-dependent protein kinase (Δ1–52PKG-Iβ). On saturation with cGMP, the radius of gyration of Δ1–52PKG-Iβ increases from 29.4 ± 0.1 Å to 40.1 ± 0.7 Å, and the maximum linear dimension increases from 90 Å ± 10% to 130 Å ± 10%. The elongation is due to a change in the interaction between structured regulatory (R) and catalytic (C) domains. A model of cGMP binding to Δ1–52PKG-Iβ indicates that elongation of Δ1–52PKG-Iβ requires binding of cGMP to the low-affinity binding site of the R domain. A comparison with cAMP-dependent protein kinase suggests that both elongation and activation require cGMP binding to both sites; cGMP binding to the low-affinity site therefore seems to be a necessary, but not sufficient, condition for both elongation and activation of Δ1–52PKG-Iβ. We also predict that there is little or no cooperativity in cGMP binding to the two sites of Δ1–52PKG-Iβ under the conditions used here. Results obtained by using the Δ1–52PKG-Iβ monomer indicate that a previously observed elongation of PKG-Iα is consistent with a pure change in the interaction between the R domain and the C domain, without alteration of the dimerization interaction. This study has revealed important features of molecular mechanisms in the biochemical network describing PKG-Iβ activation by cGMP, yielding new insight into ligand activation of cyclic nucleotide-dependent protein kinases, a class of regulatory proteins that is key to many cellular processes. |
| Related Links | http://dx.doi.org/10.1073/pnas.0534892100 |
| Ending Page | 2385 |
| Page Count | 6 |
| Starting Page | 2380 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 100 |
| Language | English |
| Publisher | The National Academy of Sciences |
| Publisher Date | 2003-03-04 |
| Access Restriction | Open |
| Rights Holder | The National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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