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-Structure paper
タイトル | An interaction network in the polymerase active site is a prerequisite for Watson-Crick base pairing in Pol γ. |
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ジャーナル・号・ページ | Sci Adv, Vol. 10, Issue 21, Page eadl3214, Year 2024 |
掲載日 | 2024年5月24日 |
著者 | Joon Park / Geoffrey K Herrmann / Arkanil Roy / Christie K Shumate / G Andrés Cisneros / Y Whitney Yin / |
PubMed 要旨 | The replication accuracy of DNA polymerase gamma (Pol γ) is essential for mitochondrial genome integrity. Mutation of human Pol γ arginine-853 has been linked to neurological diseases. Although not ...The replication accuracy of DNA polymerase gamma (Pol γ) is essential for mitochondrial genome integrity. Mutation of human Pol γ arginine-853 has been linked to neurological diseases. Although not a catalytic residue, Pol γ arginine-853 mutants are void of polymerase activity. To identify the structural basis for the disease, we determined a crystal structure of the Pol γ mutant ternary complex with correct incoming nucleotide 2'-deoxycytidine 5'-triphosphate (dCTP). Opposite to the wild type that undergoes open-to-closed conformational changes when bound to a correct nucleotide that is essential for forming a catalytically competent active site, the mutant complex failed to undergo the conformational change, and the dCTP did not base pair with its Watson-Crick complementary templating residue. Our studies revealed that arginine-853 coordinates an interaction network that aligns the 3'-end of primer and dCTP with the catalytic residues. Disruption of the network precludes the formation of Watson-Crick base pairing and closing of the active site, resulting in an inactive polymerase. |
リンク | Sci Adv / PubMed:38787958 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.37 - 3.43 Å |
構造データ | EMDB-42150, PDB-8udl: PDB-8udk: |
化合物 | ChemComp-DCP: |
由来 |
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キーワード | TRANSFERASE/DNA / Mitochondrial / DNA Polymerase / TRANSFERASE / TRANSFERASE-DNA complex |