Oral Presentation Australian & New Zealand Society of Magnetic Resonance Conference 2017

Dynamics in the Nucleosome Core Particle Arrays and CARD Filaments studied by fast MAS NMR (#62)

Konstantin Pervushin 1 , Lars Nordenskiold 1 , Wu Bin 1 , Xiangyan Shi 1 , Margaret Phillips 1
  1. Nanyang Technological University, Singapore, SINGAPORE

The chromatin structure and dynamics are critically important for the correct expression of genetic information stored in the primary sequence of DNA. The compact and folded higher order structure of chromatin takes part in repressing DNA transcription, replication and repair and is a prerequisite for these processes. Methods of solid state NMR in conjunction with novel methods of chemical residue-specific acetylation of the histones in compacted nucleosome arrays employed to characterize intramolecular dynamics in the NCP arrays. This will constitute basis for further structural understanding of chromatin and will be particularly suitable for studies of structural responses to chemical drugs and chromatin modifying protein factors affecting its stability and dynamics. Innate immune adaptor proteins are critical components of the innate immune responses through formation of oligomeric molecular scaffolds that propagate pro-inflammatory responses leading to pathogen clearance from the host. Once innate immune receptors recognize specific pathogen-associated molecular patterns, they undergo conformational changes and induce oligomerization of their corresponding innate immune adaptor proteins. These oligomers serve as a critical signal amplification scaffold propagating the activation signal through the host cell. Structural investigations of Death Domain superfamily proteins constituting the oligomerizing protomers may provide important mechanistic insights in how the innate immune activation is regulated. Solid state NMR methods can be effectively employed to characterize the processes of the structural inter-conversion in the domains and the residual dynamics in the mature filaments modulating its activity.