Structural features and interactions between transmembrane and juxtamembrane domains in membrane proteins

Reconstitution environment plays an important role in structural determination of membrane proteins. The present study explores this theme in two systems: (1) the TM domain of integrin αL/β2, a single-pass integral membrane protein that heterodimerizes in α/β pairs, and (2) CoV E protein, a single-pass integral membrane protein that forms homopentameric ion channels. Monomeric and oligomeric structural models for integrin αL/β2 and E protein were determined by solution NMR. The model of αL/β2 TM heterodimer determined herein supports the "backbone reversal" structural feature previously observed only in αIIb/β3 TM in bicelles, instead of an α-helix observed in the presence of micelles or organic solvent. Yet, it is possible that the two forms reflect different activation states of integrin. Monomeric model for CoV E protein revealed conformational flexibility with functional relevance at the C-terminal extramembrane domain. The pentameric model offered possible explanations for the ion channel activity of E protein. In both systems, we found that the alternate forms observed under different reconstitution environment may reflect alternative conformation with functional relevance.​Doctor of Philosophy (SBS