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J Mol Biol. 2014 Jan 9;426(1):43-50. doi: 10.1016/j.jmb.2013.09.025. Epub 2013 Sep 25.

Crystal structure of human poly(A) polymerase gamma reveals a conserved catalytic core for canonical poly(A) polymerases.

Author information

1
Department of Microbiology and Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0068, USA. Electronic address: yang@crystal.harvard.edu.
2
Department of Microbiology and Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0068, USA.
3
Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
4
Department of Microbiology and Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0068, USA. Electronic address: sdoublie@uvm.edu.

Abstract

In eukaryotes, the poly(A) tail added at the 3' end of an mRNA precursor is essential for the regulation of mRNA stability and the initiation of translation. Poly(A) polymerase (PAP) is the enzyme that catalyzes the poly(A) addition reaction. Multiple isoforms of PAP have been identified in vertebrates, which originate from gene duplication, alternative splicing or post-translational modifications. The complexity of PAP isoforms suggests that they might play different roles in the cell. Phylogenetic studies indicate that vertebrate PAPs are grouped into three clades termed α, β and γ, which originated from two gene duplication events. To date, all the available PAP structures are from the PAPα clade. Here, we present the crystal structure of the first representative of the PAPγ clade, human PAPγ bound to cordycepin triphosphate (3'dATP) and Ca(2+). The structure revealed that PAPγ closely resembles its PAPα ortholog. An analysis of residue conservation reveals a conserved catalytic binding pocket, whereas residues at the surface of the polymerase are more divergent.

KEYWORDS:

3′ end processing; C-terminal domain; CTD; MCMC; Markov Chain Monte Carlo; N-terminal domain; NLS; NTD; PAP; PEG; RNA recognition motif; RRM; mRNA processing; neo-PAP; nuclear localization signals; poly(A) polymerase; poly(A) polymerase gamma; polyadenylation; polyethylene glycol

PMID:
24076191
PMCID:
PMC3878066
DOI:
10.1016/j.jmb.2013.09.025
[Indexed for MEDLINE]
Free PMC Article
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