MIP channels: a general view of the cytoplasmic pore side.

ZERBETTO DE PALMA, GERARDO; CANESSA FORTUNA, AGUSTINA; CHEVRIAU, JONATHAN; ZEIDA, ARI; ALLEVA, KARINA

Congreso; Primeras jornadas virtuales SAB; 2020

Sociedad Argentina de Biofisica

Major intrinsic proteins (MIP) are transmembrane water, small solutes and ions transportchannels with proved physiological and pathophysiological importance. Generalstructural traits have been suggested from crystallographic structures and related to thegeneral function and regulation of MIP channels. In spite of this, some questionsregarding the functional and regulatory detail and diversity remain to be answered.While there is vast information about the geometry and structure of the selectivity filter(Ar/R) site and the NPA motifs and its relationship with solute selectivity and transport,there is little to none systematization on the study of the cytoplasmic end of the pore. Toaddress this issue we propose some leading questions, e.g., Do all MIP have the samegeneral structure at the cytoplasmic pore side? Can MIP be classified according to thestructure of the cytoplasmic pore side? Is this general structure related with the functionand regulation of these channels?We approached these questions analyzing all available MIP crystallographic structures,including 12 eukarya, 2 prokarya and 1 archaea. Unique wild type MIP structures at thebest resolution available were gathered from the PDB. When available, open and closedconformations were both included in the analysis. Short molecular dynamics simulationsof each structure embedded in a hydrated POPC membrane with NaCl were carried outas a previous step for comparing a set of selected structural and chemical characteristicsamong all selected MIP isoforms. Our preliminary results suggest that the pore profilescould be classified in, at least, two groups: those with a cytosolic constriction and thosewithout it.This structural knowledge about the MIP family could be of relevance to make progressboth in the understanding of gating mechanisms of these channels and the design ofspecific modulators.