Probing the Behaviour of Cas1-Cas2 upon Protospacer Binding in CRISPR-Cas Systems using Molecular Dynamics Simulations

Scientific Reports
Hua WanJianping Hu

Abstract

Adaptation in CRISPR-Cas systems enables the generation of an immunological memory to defend against invading viruses. This process is driven by foreign DNA spacer (termed protospacer) selection and integration mediated by Cas1-Cas2 protein. Recently, different states of Cas1-Cas2, in its free form and in complex with protospacer DNAs, were solved by X-ray crystallography. In this paper, molecular dynamics (MD) simulations are employed to study crystal structures of one free and two protospacer-bound Cas1-Cas2 complexes. The simulated results indicate that the protospacer binding markedly increases the system stability, in particular when the protospacer containing the PAM-complementary sequence. The hydrogen bond and binding free energy calculations explain that PAM recognition introduces more specific interactions to increase the cleavage activity of Cas1. By using principal component analysis (PCA) and intramolecular angle calculation, this study observes two dominant slow motions associated with the binding of Ca1-Cas2 to the protospacer and potential target DNAs respectively. The comparison of DNA structural deformation further implies a cooperative conformational change of Cas1-Cas2 and protospacer for the target DNA capt...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jan 1, 1997·Annual Review of Physical Chemistry·J N OnuchicP G Wolynes
May 1, 2001·Physical Review Letters·T Hatano, S Sasa
Mar 23, 2002·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Berk Hess
Apr 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tamara M OkonogiBruce H Robinson
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Mar 24, 2007·Science·Rodolphe BarrangouPhilippe Horvath
Dec 11, 2007·Journal of Bacteriology·Hélène DeveauSylvain Moineau
Aug 16, 2008·Science·Stan J J BrounsJohn van der Oost
Oct 28, 2008·Journal of Molecular Biology·Gia G MaisuradzeHarold A Scheraga
Jul 25, 2009·Nucleic Acids Research·R LaveryK Zakrzewska
Aug 4, 2009·Trends in Biochemical Sciences·John van der OostStan J J Brouns
Mar 13, 2010·Nucleic Acids Research·Allison J DePaulEric J Sorin
Nov 5, 2010·Nature·Josiane E GarneauSylvain Moineau
May 10, 2011·Nature Reviews. Microbiology·Kira S MakarovaEugene V Koonin
Jun 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ekaterina SemenovaKonstantin Severinov
May 5, 2012·PloS One·Daan C SwartsStan J J Brouns
Jul 12, 2012·Nature Communications·Kirill A DatsenkoEkaterina Semenova
Dec 12, 2012·Physical Chemistry Chemical Physics : PCCP·Hua WanShan Chang
Sep 26, 2013·Methods in Molecular Biology·Charles C David, Donald J Jacobs
Apr 29, 2014·Molecular Cell·Rodolphe Barrangou, Luciano A Marraffini
May 6, 2014·Nature Structural & Molecular Biology·James K NuñezJennifer A Doudna
May 23, 2014·Journal of Chemical Information and Modeling·Rashmi KumariAndrew Lynn
Mar 4, 2015·Journal of Chemical Information and Modeling·Hua WanXu-hong Tian
Oct 28, 2015·Nature·James K NuñezJennifer A Doudna
Jul 13, 2016·Nature Biotechnology·Luca PinelloGuo-Cheng Yuan
Apr 8, 2017·Science·Simon A JacksonStan J J Brouns
Jul 22, 2017·Science·Addison V WrightJennifer A Doudna
Nov 18, 2017·Nucleic Acids Research·Yan ZengJizhong Lou
Dec 19, 2017·PLoS Computational Biology·Alexander MartynovIaroslav Ispolatov
Jul 18, 2018·The European Physical Journal. E, Soft Matter·See-Chuan YamKhian-Hooi Chew

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoretic mobility shift assay
PCA

Software Mentioned

PC2
GROMACS
mmpbsa
NAMD
FEL
CHARMM27
Curves
CRISPResso
VMD

Related Concepts

Related Feeds

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

Virology & CRISPR

This feed focuses on the virology of CRISPR and its use in developing CRISPR-Cas systems. Discover the latest research here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.