Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Poster Abstracts

10-POS Board 10 MOLECULAR MECHANISMS OF CARDIAC REGULATION THROUGH MODIFYING INTRINSICALLY DISORDERED REGIONS IN MYOFILAMENT PROTEINS Peter Kekenes-Huskey ; 1 Loyola University Chicago, Maywoo, IL, USA The heart adapts to cardiac demand through a variety of mechanisms. Some of these adaptions include chemical modifications of myofilament proteins responsible for cell contraction. Interestingly, many of these chemical modifications, such as phosphorylation and acetylation, are found in unstructured, or intrinsically-disordered, regions of proteins. However, it has been surprisingly difficult to determine how modifications of intrinsically disordered regions (IDRs) influence the function of their parent proteins or the myofilament as a whole. We hypothesized that regulation of myofilaments proteins via their IDRs occurs because post-translational, e.g. chemical, modifications (PTMs) alter their conformation ensembles. To evaluate this hypothesis, we used molecular dynamics and continuum models for simulating a representative IDR to describe its conformation ensemble before and after modification. Our results indicate that local changes in the physicochemical properties of an IDR via chemical modification can influence global ensemble properties. These findings provide an important clue into the mechanisms of myofilament protein regulation through PTMs.

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