| Title |
Large Extent of Disorder in Adenomatous Polyposis Coli Offers a Strategy to Guard Wnt Signalling against Point Mutations
|
|---|---|
| Published in |
PLOS ONE, October 2013
|
| DOI | 10.1371/journal.pone.0077257 |
| Pubmed ID | |
| Authors |
David P. Minde, Martina Radli, Federico Forneris, Madelon M. Maurice, Stefan G. D. Rüdiger |
| Abstract |
Mutations in the central region of the signalling hub Adenomatous Polyposis Coli (APC) cause colorectal tumourigenesis. The structure of this region remained unknown. Here, we characterise the Mutation Cluster Region in APC (APC-MCR) as intrinsically disordered and propose a model how this structural feature may contribute to regulation of Wnt signalling by phosphorylation. APC-MCR was susceptible to proteolysis, lacked α-helical secondary structure and did not display thermal unfolding transition. It displayed an extended conformation in size exclusion chromatography and was accessible for phosphorylation by CK1ε in vitro. The length of disordered regions in APC increases with species complexity, from C. elegans to H. sapiens. We speculate that the large disordered region harbouring phosphorylation sites could be a successful strategy to stabilise tight regulation of Wnt signalling against single missense mutations. |
Mendeley readers
The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Unknown | 52 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 20 | 38% |
| Student > Master | 13 | 25% |
| Researcher | 6 | 11% |
| Professor > Associate Professor | 3 | 6% |
| Lecturer > Senior Lecturer | 1 | 2% |
| Other | 3 | 6% |
| Unknown | 7 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 20 | 38% |
| Agricultural and Biological Sciences | 17 | 32% |
| Medicine and Dentistry | 2 | 4% |
| Chemistry | 2 | 4% |
| Mathematics | 1 | 2% |
| Other | 4 | 8% |
| Unknown | 7 | 13% |