Crystal Structure of Human Poly(A) Polymerase Gamma Reveals a Conserved Catalytic Core for Canonical Poly(A) Polymerases

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• 作者：Qin Yang ; Lydia W.M. Nausch ; Georges Martin ; Walter Keller ; Sylvie Doubli茅
• 关键词：PAP ; poly(A) polymerase ; RRM ; RNA recognition motif ; CTD ; C-terminal domain ; NTD ; N-terminal domain ; NLS ; nuclear localization signals ; PEG ; polyethylene glycol ; MCMC ; Markov Chain Monte Carlo
• 刊名：Journal of Molecular Biology
• 出版年：9 January, 2014
• 年：2014
• 卷：426
• 期：1
• 页码：43-50
• 全文大小：722 K

文摘

In eukaryotes, the poly(A) tail added at the 3鈥?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 伪, 尾 and 纬, which originated from two gene duplication events. To date, all the available PAP structures are from the PAP伪 clade. Here, we present the crystal structure of the first representative of the PAP纬 clade, human PAP纬 bound to cordycepin triphosphate (3鈥瞕ATP) and Ca^2 +. The structure revealed that PAP纬 closely resembles its PAP伪 ortholog. An analysis of residue conservation reveals a conserved catalytic binding pocket, whereas residues at the surface of the polymerase are more divergent.