| Disease mutations in disordered regions--exception to the rule? | |
| | |
MedLine Citation:
|
PMID: 22080206 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Intrinsically disordered proteins (IDPs) have been implicated in a number of human diseases, including cancer, diabetes, neurodegenerative and cardiovascular disorders. Although for some of these conditions molecular mechanisms are now better understood, the big picture connecting distinct structural properties and functional repertoire of IDPs to pathogenesis and disease progression is still incomplete. Recent studies suggest that signaling and regulatory roles carried out by IDPs require them to be tightly regulated, and that altered IDP abundance may lead to disease. Here, we propose another link between IDPs and disease that takes into account disease-associated missense mutations located in the intrinsically disordered regions. We argue that such mutations are more prevalent and have larger functional impact than previously thought. In addition, we demonstrate that deleterious amino acid substitutions that cause disorder-to-order transitions are particularly enriched among disease mutations compared to neutral polymorphisms. Finally, we discuss potential differences in functional outcomes between disease mutations in ordered and disordered regions, and challenge the conventional structure-centric view of missense mutations. |
| | |
Authors:
|
Vladimir Vacic; Lilia M Iakoucheva |
Related Documents
:
|
22083296 - Angiogenesis and vasculopathy in systemic sclerosis: evolving concepts. 22474316 - Mitral valve disease in circulation and the circulation subspecialty journals. 21747866 - Genetic variability in susceptibility to occupational respiratory sensitization. 21714896 - Dosim: an r package for similarity between diseases based on disease ontology. 2391726 - The causes of death in an elderly african population. 9590426 - Glutathione content of colonic mucosa: evidence for oxidative damage in active ulcerati... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review Date: 2011-11-14 |
Journal Detail:
|
Title: Molecular bioSystems Volume: 8 ISSN: 1742-2051 ISO Abbreviation: Mol Biosyst Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2011-12-02 Completed Date: 2012-03-20 Revised Date: 2013-05-23 |
Medline Journal Info:
|
Nlm Unique ID: 101251620 Medline TA: Mol Biosyst Country: England |
Other Details:
|
Languages: eng Pagination: 27-32 Citation Subset: IM |
Affiliation:
|
Department of Computer Science, Columbia University, New York, NY 10027, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Databases, Protein Disease / genetics* Humans Mutation / genetics* Protein Conformation Protein Folding* Proteins / chemistry*, genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
R01 HD065288/HD/NICHD NIH HHS; R01 HD065288/HD/NICHD NIH HHS; R01 HD065288-02/HD/NICHD NIH HHS; R01 MH091350/MH/NIMH NIH HHS; R01 MH091350/MH/NIMH NIH HHS; R01 MH091350-02/MH/NIMH NIH HHS; R01 MH091350-03/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: 4-Component relativistic magnetically induced current density using London atomic orbitals.
Next Document: Chemically modified diamond-like carbon (DLC) for protein enrichment and profiling by MALDI-MS.