Related Experiment Video
Updated: Mar 15, 2026
09:16
A Simple and Efficient Approach to Construct Mutant Vaccinia Virus Vectors
Published on: October 30, 2016
11.9K
Structural analysis of point mutations at the Vaccinia virus A20/D4 interface
Céline Contesto-Richefeu1, Nicolas Tarbouriech2, Xavier Brazzolotto3
1Unité de Virologie, Institut de Recherche Biomédicale des Armées, BP 73, 91223 Brétigny-sur-Orge CEDEX, France.
Acta Crystallographica. Section F, Structural Biology Communications
|September 8, 2016
Summary
The Vaccinia virus DNA polymerase cofactor, D4/A20, is crucial for DNA synthesis. New crystal structures reveal how specific mutations affect the D4/A20 interface, aiding in the development of antiviral drugs.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- The Vaccinia virus polymerase holoenzyme comprises E9 (DNA polymerase), D4 (uracil-DNA glycosylase), and A20.
- The D4/A20 heterodimer functions as an essential DNA polymerase cofactor for processive DNA synthesis.
Purpose of the Study:
- To elucidate the structural basis of D4/A20 complex formation and stability.
- To investigate the role of specific residues (Arg167, Pro173 of D4, and Trp43 of A20) in mediating cation-π interactions at the dimerization interface.
Main Methods:
- X-ray crystallography was used to determine the structures of three D4/A20 mutants (D4-R167A/A201-50, D4-P173G/A201-50, and D4/A201-50-W43A).
- Analysis of atomic solvation parameters and cation-π interactions at the D4/A20 interface was performed.
Main Results:
- The crystal structures confirmed the importance of Arg167, Pro173, and Trp43 for D4/A20 complex formation.
- The study highlighted the significance of Pro173's constrained conformation for complex stability.
- Biochemical data were corroborated, and new structural insights were gained.
Conclusions:
- The findings provide a detailed understanding of the D4/A20 interface and the role of specific residues in complex stability.
- These structures offer valuable information for the rational design and optimization of molecules targeting the D4/A20 interface for therapeutic purposes.
Related Concept Videos
01:30Point and Frameshift Mutations
1.5K
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
1.5K
02:28Leaky Scanning
5.8K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.8K
00:36Viral Mutations
40.6K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
40.6K
01:18Mutations in Microorganisms
999
Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
999