7p9j

Prim-Pol Domain of CRISPR-associated Prim-Pol (CAPP) from Marinitoga sp. 1137 - Primer Initiation Complex

spinqualitylabelsall models 7p9j, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7p9j is a 4 chain structure with sequence from Marinitoga sp. 1137 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: CO, DZ4, GTP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function H2J4R1_MARPK Publication Abstract from PubMed During the initiation of DNA replication, oligonucleotide primers are synthesized de novo by primases and are subsequently extended by replicative polymerases to complete genome duplication. The primase-polymerase (Prim-Pol) superfamily is a diverse grouping of primases, which includes replicative primases and CRISPR-associated primase-polymerases (CAPPs) involved in adaptive immunity(1-3). Although much is known about the activities of these enzymes, the precise mechanism used by primases to initiate primer synthesis has not been elucidated. Here we identify the molecular bases for the initiation of primer synthesis by CAPP and show that this mechanism is also conserved in replicative primases. The crystal structure of a primer initiation complex reveals how the incoming nucleotides are positioned within the active site, adjacent to metal cofactors and paired to the templating single-stranded DNA strand, before synthesis of the first phosphodiester bond. Furthermore, the structure of a Prim-Pol complex with double-stranded DNA shows how the enzyme subsequently extends primers in a processive polymerase mode. The structural and mechanistic studies presented here establish how Prim-Pol proteins instigate primer synthesis, revealing the requisite molecular determinants for primer synthesis within the catalytic domain. This work also establishes that the catalytic domain of Prim-Pol enzymes, including replicative primases, is sufficient to catalyse primer formation. Molecular basis for the initiation of DNA primer synthesis.,Li AWH, Zabrady K, Bainbridge LJ, Zabrady M, Naseem-Khan S, Berger MB, Kolesar P, Cisneros GA, Doherty AJ Nature. 2022 May 4. pii: 10.1038/s41586-022-04695-0. doi:, 10.1038/s41586-022-04695-0. PMID:35508653 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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