Peptide Sequence Influence on the Conformational Dynamics and DNA binding of the Intrinsically Disordered AT-Hook 3 Peptide.
Alyssa GarabedianAlexander BoluferFenfei LengFrancisco Fernandez LimaPublished in: Scientific reports (2018)
The intrinsically disordered ATHP3 was studied at native conditions and in complex with DNA using single amino acid substitutions and high-resolution ion mobility spectrometry coupled to mass spectrometry (trapped IMS-MS). Results showed that ATHP3 can exist in multiple conformations at native conditions (at least 10 conformers were separated), with a variety of proline cis/trans orientations, side chain orientations and protonation sites. When in complex with AT rich DNA hairpins, the -RGRP- core is essential for stabilizing the ATHP3: DNA complex. In particular, the arginine in the sixth position plays an important role during binding to AT-rich regions of hairpin DNA, in good agreement with previous NMR and X-ray data. Mobility based correlation matrices are proposed as a way to reveal differences in structural motifs across the peptide mutants based on the conformational space and relative conformer abundance.
Keyphrases
- high resolution
- single molecule
- circulating tumor
- mass spectrometry
- cell free
- dna binding
- amino acid
- molecular dynamics
- nucleic acid
- molecular dynamics simulations
- magnetic resonance
- dna methylation
- nitric oxide
- gas chromatography
- multiple sclerosis
- ms ms
- liquid chromatography
- computed tomography
- circulating tumor cells
- transcription factor
- big data
- machine learning
- microbial community
- tandem mass spectrometry
- genome wide
- single cell
- capillary electrophoresis