Rationalisation of the differences between APOBEC3G structures from crystallography and NMR studies by molecular dynamics simulations.

PloS One
Flavia AutoreHendrik Huthoff

Abstract

The human APOBEC3G (A3G) protein is a cellular polynucleotide cytidine deaminase that acts as a host restriction factor of retroviruses, including HIV-1 and various transposable elements. Recently, three NMR and two crystal structures of the catalytic deaminase domain of A3G have been reported, but these are in disagreement over the conformation of a terminal beta-strand, beta2, as well as the identification of a putative DNA binding site. We here report molecular dynamics simulations with all of the solved A3G catalytic domain structures, taking into account solubility enhancing mutations that were introduced during derivation of three out of the five structures. In the course of these simulations, we observed a general trend towards increased definition of the beta2 strand for those structures that have a distorted starting conformation of beta2. Solvent density maps around the protein as calculated from MD simulations indicated that this distortion is dependent on preferential hydration of residues within the beta2 strand. We also demonstrate that the identification of a pre-defined DNA binding site is prevented by the inherent flexibility of loops that determine access to the deaminase catalytic core. We discuss the implica...Continue Reading

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Citations

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Jun 26, 2021·The Journal of Biological Chemistry·Shurong HouCelia A Schiffer

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Methods Mentioned

BETA
deamination
NMR
PCA
electrophoresis

Software Mentioned

VMD
GROMOS
coffee
PyMOL
POPS
GROMOS96
Dynamite
GROMACS

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