Quaternary arrangements of membrane proteins: an aquaporin case.

Abstract

Integral polytopic α-helical membrane transporters and aquaporins move and distribute various molecules and dispose of or compartmentalize harmful elements that gather in living cells. The view shaped nearly 25 years ago states that integrating these proteins into cellular membranes can be considered a two-stage process, with hydrophobic core folding into α-helices across membranes to form functional entities (Popot and Engelman, 1990; Biochemistry29, 4031-4037). Since then, a large body of evidence cemented the roles of structural properties of membrane proteins and bilayer solvent components in forming functional assemblies. This mini-review updates our understanding of multifaced factors, which underlie transporters integration and oligomerization, focusing on water-permeating aquaporins. This work also elaborates on how individual monomers of bacterial and mammalian aquaporin tetramers, interact with each other, and how tetramers form contacts with lipids after being embedded in lipid bilayers of known composition, which mimics bacterial and mammalian membranes. Although this mini-review describes findings acquired using current methods, the view is open to how to extend this knowledge through, e.g. single-molecule-based and in situ cryogenic-electron tomography techniques. These and other methods could unravel the sources of entropy for membrane protein assemblies and pathways underlying integration, folding, oligomerization and quaternary structure formation with binding partners. We could expect that these exceedingly interdisciplinary approaches will form the basis for creating optimized transport systems, which could inspire bioengineering to develop a sustainable and healthy society.