Evolutionary clues to DNA polymerase III beta clamp structural mechanisms

Neuwald, A. F. (August 2003) Evolutionary clues to DNA polymerase III beta clamp structural mechanisms. Nucleic Acids Research, 31 (15). pp. 4503-4516. ISSN 0305-1048

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Abstract

The prokaryotic DNA polymerase III beta homodimeric clamp links the replication complex to DNA during polynucleotide synthesis. This clamp is loaded onto DNA and unloaded by the clamp loader complex, the delta subunit of which by itself can bind to and open the clamp. beta Clamps from diverse bacteria were examined using contrast hierarchical alignment and interaction network (CHAIN) analysis, a statistical approach that categorizes and measures the evolutionary constraints imposed on protein sequences by natural selection. Some constraints are subtle inasmuch as they are unique to certain bacteria. Examination of corresponding molecular interactions within structures of the Escherichia coli beta dimeric and delta-beta complexes reveals that N320, Y323 and R176, which are subject to very strong constraints, form a substructure that may serve as a platform for leveraging and directing delta-induced conformational changes. N320 may play a prominent role, as it is strategically situated between this substructure and regions linked to delta binding and opening of beta's dimeric interface. R176 appears to act as a relay between the delta binding site and the clamp's central hole. Other residues subject to strong constraints are likewise associated with structurally important features. For example, two pairs of interacting residues, R269/E304 and K74/E300, form salt bridges at the dimeric interface, while the C-terminal residues M362, P363, M364 and R365 appear to play key roles in delta binding. Q149 and K198 appear to sense DNA within the clamp's central hole while other residues may relay this information to the delta binding site. Mutagenesis experiments designed to explore possible mechanisms are proposed.

Item Type:	Paper
Uncontrolled Keywords:	ESCHERICHIA-COLI CRYSTAL-STRUCTURE SLIDING CLAMPS DELTA-SUBUNIT NUCLEOTIDE EXCHANGE REPLICATION MACHINE PROCESSIVITY FACTOR HOLOENZYME PROTEINS LOADER
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > DNA polymerase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > alignment > sequence alignment bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:	Neuwald, Andrew F.
Communities:	CSHL labs > Neuwald lab
Depositing User:	Matt Covey
Date:	August 2003
Date Deposited:	02 Apr 2013 16:06
Last Modified:	02 Apr 2013 16:06
PMCID:	PMC169876
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27966

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