Nanoscale regulation of Ca2+ dependent phase transitions and real-time dynamics of SAP97/hDLG

Abstract

Synapse associated protein-97/Human Disk Large (SAP97/hDLG) is a conserved, alternatively spliced, modular, scaffolding protein critical in regulating the molecular organization of cell-cell junctions in vertebrates. We confirm that the molecular determinants of first order phase transition of SAP97/hDLG is controlled by morpho-functional changes in its nanoscale organization. Furthermore, the nanoscale molecular signatures of these signalling islands and phase transitions are altered in response to changes in cytosolic Ca2+. Additionally, exchange kinetics of alternatively spliced isoforms of the intrinsically disordered region in SAP97/hDLG C-terminus shows differential sensitivities to Ca2+ bound Calmodulin, affirming that the molecular signatures of local phase transitions of SAP97/hDLG depends on their nanoscale heterogeneity and compositionality of isoforms.

Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu

“…There might be a possibility that the cellular environment, sequence and structure of protein might dictate protein aggregation either from liquid condensate and/or small/large mesoscopic clusters. Moreover, there can also be a rearrangement of existing molecular machineries and component systems in cells that may give rise to condensates of a few tens of nanometers in diameter 37 , 106 .…”