Transmembrane Helices Tilt, Bend, Slide, Torque, and Unwind between Functional States of Rhodopsin.

Zhong Ren,Rohith Balusu,Peter X Ren,Xiaojing Yang

doi:10.1038/srep34129

Abstract

The seven-helical bundle of rhodopsin and other G-protein coupled receptors undergoes structural rearrangements as the transmembrane receptor protein is activated. These structural changes are known to involve tilting and bending of various transmembrane helices. However, the cause and effect relationship among structural events leading to a cytoplasmic crevasse for G-protein binding is less well defined. Here we present a mathematical model of the protein helix and a simple procedure to determine multiple parameters that offer precise depiction of a helical conformation. A comprehensive survey of bovine rhodopsin structures shows that the helical rearrangements during the activation of rhodopsin involve a variety of angular and linear motions such as torsion, unwinding, and sliding in addition to the previously reported tilting and bending. These hitherto undefined motion components unify the results obtained from different experimental approaches, and demonstrate conformational similarity between the active opsin structure and the photoactivated structures in crystallo near the retinal anchor despite their marked differences.

Highlights

The helix is the most common secondary structure found in the transmembrane (TM) segments of membrane proteins
Least-square fitting of this formula to the atomic coordinates of bovine rhodopsin in Protein Data Bank (PDB) produces a set of geometric parameters that numerically define the conformation of each helix segment in a rhodopsin structure
Our findings suggest that TM helices may transmit force via torsional motions, which are often coupled with helical winding and unwinding

Summary

Introduction

The helix is the most common secondary structure found in the transmembrane (TM) segments of membrane proteins. Some TM segments undergo significant torsional motions, that is, a rigid body rotation about the helical axis. We find a strong correlation between these movements of helices and the functional states of rhodopsin and opsin These findings lead us to hypothesize that the TM segments of rhodopsin, and presumably other GPCRs, act as electromechanical parts that interconvert between an inactive but armed state in dark and the active state characterized by the outward tilting of TM6, as the G-protein binding crevasse opens. Angular motions of helices such as torsion, overwinding and unwinding play a structural role in signal transduction due to the mechanical property of protein helices

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