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Probing The Structure And Dynamics Of Nucleosomes Using Atomic Force Microscopy Imaging
Published on: January 31, 2019
Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction
Yannick Bulliard1, Iñigo Narvaiza, Alessandro Bertero
1School of Life Sciences and Frontiers-in-Genetics National Program, Ecole Polytechnique Fe´de´rale de Lausanne,1015 Lausanne, Switzerland.
Journal of Virology
|December 3, 2010
Summary
Human APOBEC3A (A3A) and APOBEC3G (A3G) enzymes have different targets. Structural differences in A3A
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- The human APOBEC3 (A3) enzyme family plays a role in inhibiting mobile genetic elements.
- APOBEC3A (A3A) inhibits LINE-1 and adeno-associated virus type 2 (AAV-2), while APOBEC3G (A3G) inhibits retroviruses.
- The basis for this differential target specificity among A3 enzymes is not well understood.
Purpose of the Study:
- To investigate the structural basis for the differential target specificity of APOBEC3A (A3A) and APOBEC3G (A3G).
- To identify key amino acid residues responsible for A3A's ability to inhibit LINE-1 and AAV-2.
Main Methods:
- Modeled the structure of A3A based on homology with A3G.
- Sequenced A3A from 11 nonhuman primate orthologues.
- Performed mutational analysis of A3A to assess its restriction of LINE-1, AAV-2, and plasmid DNA, and its editing of single-stranded DNA.
Main Results:
- A single-stranded DNA-docking groove near the A3A catalytic site is crucial for its function.
- Amino acid variations within this groove between A3A and A3G influence polynucleotide binding.
- Transferring specific A3A residues to A3G conferred LINE-1 and AAV-2 inhibitory activity to A3G.
Conclusions:
- Structural features of the polynucleotide-binding groove dictate the target specificity of APOBEC3 enzymes.
- The differential inhibition of LINE-1 and AAV-2 by A3A is attributed to specific amino acid differences in the DNA-binding groove.
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