English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/153515
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

A common structural scaffold in CTD phosphatases that supports distinct catalytic mechanisms

AuthorsPons, Tirso ; Paramonov, Ida; Boullosa, César; Ibáñez, Kristina; Rojas, A. M. ; Valencia, Alfonso
KeywordsStructure comparison
RNA poly merase II carboxyl-terminal domain
Protein phosphatases
Catalytic mechanism
HAD superfamily
Prolyl cis/trans isomerization
Oxidative stress
Neurodegeneration
Mental disorders
Alzheimer’s disease
Parkinson’s disease
Schizophrenia
Issue DateJan-2014
PublisherWiley-Liss
CitationProteins 82(1): 103–118 (2014)
AbstractThe phosphorylation and dephosphorylation of the carboxyl-terminal domain (CTD) of the largest RNA polymerase II (RNAPII) subunit is a critical regulatory checkpoint for transcription and mRNA processing. This CTD is unique to eukaryotic organisms and it contains multiple tandem-repeats with the consensus sequence Tyr1–Ser2–Pro3–Thr4–Ser5–Pro6–Ser7. Traditionally, CTD phosphatases that use metal-ion-independent (cysteine-based) and metal-ion-assisted (aspartate-based) catalytic mechanisms have been considered to belong to two independent groups. However, using structural comparisons we have identified a common structural scaffold in these two groups of CTD phosphatases. This common scaffold accommodates different catalytic processes with the same substrate specificity, in this case phospho-serine/threonine residues flanked by prolines. Furthermore, this scaffold provides a structural connection between two groups of protein tyrosine phosphatases (PTPs): Cys-based (classes I, II, and III) and Asp-based (class IV) PTPs. Redundancy in catalytic mechanisms is not infrequent and may arise in specific biological settings. To better understand the activity of the CTD phosphatases, we combined our structural analyses with data on CTD phosphatase expression in different human and mouse tissues. The results suggest that aspartate- and cysteine-based CTD-dephosphorylation acts in concert during cellular stress, when high levels of reactive oxygen species can inhibit the nucleophilic function of the catalytic cysteine, as occurs in mental and neurodegenerative disorders like schizophrenia, Alzheimer's and Parkinson's diseases. Moreover, these findings have significant implications for the study of the RNAPII-CTD dephosphorylation in eukaryotes. Proteins 2014; 82:103–118. © 2013 Wiley Periodicals, Inc.
Publisher version (URL)http://doi.org/10.1002/prot.24376
URIhttp://hdl.handle.net/10261/153515
DOI10.1002/prot.24376
ISSN0887-3585
E-ISSN1097-0134
Appears in Collections:(IBIS) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.