Chemistry Commons^™

Continuum Dynamics And Statistical Correction Of Compositional Heterogeneity In Multivalent Idp Oligomers Resolved By Single-Particle Em, Barmak Mostofian, Russell Mcfarland, Aiden Estelle, Jesse Howe, Elisar J. Barbar, Steve L. Reichow, Daniel M. Zuckerman

Chemistry Faculty Publications and Presentations

Multivalent intrinsically disordered protein (IDP) complexes are prevalent in biology and act in regulation of diverse processes, including transcription, signaling events, and the assembly and disassembly of complex macromolecular architectures. These systems pose significant challenges to structural investigation, due to continuum dynamics imparted by the IDP and compositional heterogeneity resulting from characteristic low-affinity interactions. Here, we developed a modular pipeline for automated single-particle electron microscopy (EM) distribution analysis of common but relatively understudied semi-ordered systems: 'beads-on-a-string' assemblies, composed of IDPs bound at multivalent sites to the ubiquitous ∼20kDacross-linking hub protein LC8. This approach quantifies conformational geometries and compositional heterogeneity on …