Summary: Bacterial DNA polymerase III alpha NTPase domain
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This is the Wikipedia entry entitled "DNA polymerase III holoenzyme". More...
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DNA polymerase III holoenzyme Edit Wikipedia article
DNA polymerase III holoenzyme is the primary enzyme complex involved in prokaryotic DNA replication. It was discovered by Thomas Kornberg (son of Arthur Kornberg) and Malcolm Gefter in 1970. The complex has high processivity (i.e. the number of nucleotides added per binding event) and, specifically referring to the replication of the E.coli genome, works in conjunction with four other DNA polymerases (Pol I, Pol II, Pol IV, and Pol V). Being the primary holoenzyme involved in replication activity, the DNA Pol III holoenzyme also has proofreading capabilities that corrects replication mistakes by means of exonuclease activity reading 3'â†’5' and synthesizing 5'â†’3'. DNA Pol III is a component of the replisome, which is located at the replication fork.
The replisome is composed of the following:
- 2 DNA Pol III enzymes, each comprising Î±, Îµ and Î¸ subunits. (It has been proven that there is a third copy of Pol III at the replisome.)
- 2 Î² units (dnaN) which act as sliding DNA clamps, they keep the polymerase bound to the DNA.
- 2 Ï„ units (dnaX) which act to dimerize two of the core enzymes (Î±, Îµ, and Î¸ subunits).
- 1 Î³ unit (also dnaX) which acts as a clamp loader for the lagging strand Okazaki fragments, helping the two Î² subunits to form a unit and bind to DNA. The Î³ unit is made up of 5 Î³ subunits which include 3 Î³ subunits, 1 Î´ subunit (holA), and 1 Î´' subunit (holB). The Î´ is involved in copying of the lagging strand.
- Î§ (holC) and Î¨ (holD) which form a 1:1 complex and bind to Î³ or Ï„. X can also mediate the switch from RNA primer to DNA.
DNA polymerase III synthesizes base pairs at a rate of around 1000 nucleotides per second. DNA Pol III activity begins after strand separation at the origin of replication. Because DNA synthesis cannot start de novo, an RNA primer, complementary to part of the single-stranded DNA, is synthesized by primase (an RNA polymerase):
--------> * * * * ! ! ! ! _ _ _ _ _ _ _ _ | RNA | <--ribose (sugar)-phosphate backbone G U A U | Pol | <--RNA primer * * * * |_ _ _ _| <--hydrogen bonding C A T A G C A T C C <--template ssDNA (single-stranded DNA) _ _ _ _ _ _ _ _ _ _ <--deoxyribose (sugar)-phosphate backbone $ $ $ $ $ $ $ $ $ $
Addition onto 3'OH
As replication progresses and the replisome moves forward, DNA polymerase III arrives at the RNA primer and begins replicating the DNA, adding onto the 3'OH of the primer:
* * * * ! ! ! ! _ _ _ _ _ _ _ _ | DNA | <--deoxyribose (sugar)-phosphate backbone G U A U | Pol | <--RNA primer * * * * |_III_ _| <--hydrogen bonding C A T A G C A T C C <--template ssDNA (single-stranded DNA) _ _ _ _ _ _ _ _ _ _ <--deoxyribose (sugar)-phosphate backbone $ $ $ $ $ $ $ $ $ $
Synthesis of DNA
DNA polymerase III will then synthesize a continuous or discontinuous strand of DNA, depending if this is occurring on the leading or lagging strand (Okazaki fragment) of the DNA. DNA polymerase III has a high processivity and therefore, synthesizes DNA very quickly. This high processivity is due in part to the Î²-clamps that "hold" onto the DNA strands.
-----------> * * * * ! ! ! ! $ $ $ $ $ $ _ _ _ _ _ _ _ _ _ _ _ _ _ _| DNA | <--deoxyribose (sugar)-phosphate backbone G U A U C G T A G G| Pol | <--RNA primer * * * * * * * * * *|_III_ _| <--hydrogen bonding C A T A G C A T C C <--template ssDNA (single-stranded DNA) _ _ _ _ _ _ _ _ _ _ <--deoxyribose (sugar)-phosphate backbone $ $ $ $ $ $ $ $ $ $
Removal of primer
After replication of the desired region, the RNA primer is removed by DNA polymerase I via the process of nick translation. The removal of the RNA primer allows DNA ligase to ligate the DNA-DNA nick between the new fragment and the previous strand. DNA polymerase I & III, along with many other enzymes are all required for the high fidelity, high-processivity of DNA replication.
- Reyes-Lamothe R, Sherratt D, Leake M (2010). "Stoichiometry and Architecture of Active DNA Replication Machinery in Escherichia Coli". Science. 328 (5977): 498â€“501. doi:10.1126/science.1185757. PMC 2859602. PMID 20413500.
- Olson MW, Dallmann HG, McHenry CS (December 1995). "DnaX complex of Escherichia coli DNA polymerase III holoenzyme. The chi psi complex functions by increasing the affinity of tau and gamma for delta.delta' to a physiologically relevant range". J. Biol. Chem. 270 (49): 29570â€“7. doi:10.1074/jbc.270.49.29570. PMID 7494000.
- Kelman Z, O'Donnell M (1995). "DNA polymerase III holoenzyme: structure and function of a chromosomal replicating machine". Annu. Rev. Biochem. 64: 171â€“200. doi:10.1146/annurev.bi.64.070195.001131. PMID 7574479.
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Bacterial DNA polymerase III alpha NTPase domain Provide feedback
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Internal database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR011708
This is a conserved region found in the the DNA polymerase III alpha subunit, ( EC ). DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. This DNA polymerase also exhibits 3' to 5' exonuclease activity. The alpha chain is the DNA polymerase [ PUBMED:9685491 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||3'-5' exonuclease activity (GO:0008408)|
|Biological process||DNA replication (GO:0006260)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan contains a diverse set of nucleotidyltransferase enzymes.
The clan contains the following 33 members:AbiEii Adenyl_cycl_N Adenyl_transf Aminoglyc_resit DNA_pol3_alpha DNA_pol_B_palm DUF2204 DUF294 DUF4269 DUF6036 DZF GlnE GrpB LicD Mab-21 MdcG Nrap Nrap_D4 NTF-like NTP_transf_2 NTP_transf_5 NTP_transf_6 NTP_transf_7 NTP_transf_8 Polbeta PolyA_pol Pox_polyA_pol RelA_SpoT RlaP RsfS SMODS Tam41_Mmp37 TUTase
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Seed source:||Pfam-B111 (Release 14.0)|
|Author:||Studholme DJ , Bateman A|
|Number in seed:||88|
|Number in full:||15863|
|Average length of the domain:||240.80 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||22.64 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DNA_pol3_alpha domain has been found. There are 22 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
|Protein||Predicted structure||External Information|
|P10443||View 3D Structure||Click here|
|P9WNT5||View 3D Structure||Click here|
|P9WNT7||View 3D Structure||Click here|
|Q2G1Z8||View 3D Structure||Click here|
|Q9F1K0||View 3D Structure||Click here|