The Structure of Fcp1, an Essential RNA Polymerase II CTD Phosphatase

Journal Article · Fri Mar 27 04:00:00 EDT 2009 · Mol. Cell

DOI:https://doi.org/10.1016/j.molcel.2008.09.021· OSTI ID:1007068

Ghosh, A; Shuman, S; Lima, C D ^[1]

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1. SKI

Kinases and phosphatases regulate mRNA synthesis and processing by phosphorylating and dephosphorylating the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. Fcp1 is an essential CTD phosphatase that preferentially hydrolyzes Ser2-PO{sub 4} of the tandem YSPTSPS CTD heptad array. Fcp1 crystal structures were captured at two stages of the reaction pathway: a Mg-BeF{sub 3} complex that mimics the aspartylphosphate intermediate and a Mg-AlF{sub 4}{sup -} complex that mimics the transition state of the hydrolysis step. Fcp1 is a Y-shaped protein composed of an acylphosphatase domain located at the base of a deep canyon formed by flanking modules that are missing from the small CTD phosphatase (SCP) clade: an Fcp1-specific helical domain and a C-terminal BRCA1 C-terminal (BRCT) domain. The structure and mutational analysis reveals that Fcp1 and Scp1 (a Ser5-selective phosphatase) adopt different CTD-binding modes; we surmise the CTD threads through the Fcp1 canyon to access the active site.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1007068
• Journal Information: Mol. Cell, Journal Name: Mol. Cell Journal Issue: (4) ; 11, 2008 Vol. 32; ISSN 1097-2765
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
HYDROLYSIS
PHOSPHATASES
PHOSPHOTRANSFERASES
PROCESSING
PROTEINS
RNA POLYMERASES
SYNTHESIS