Deconstructing Membrane Proteins

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Science  25 Feb 2005:
Vol. 307, Issue 5713, pp. 1173
DOI: 10.1126/science.307.5713.1173a

Progress in understanding how a protein finds its three-dimensional structure in seconds has been hard-won, and some of the successes have come from studying the intermediate stages (or lack thereof) of protein structures when they are stressed by pH, denaturants, or mechanical force. The historic nomenclature of structures (primary, secondary, and so forth) largely reflects the current thinking that helices form early and relatively independently, that interactions between helices help steer the folding trajectory (by clamping posts and beams) into domains, and that fitting amino acid side chains into pockets (like tenons and mortises) locks everything into place. Most unfolding studies have avoided the complications of membranes; structure determination of intact membrane proteins is not easy, and the study of pH- or denaturant-treated membrane proteins is truly daunting.

Cisneros et al. have applied mechanical force to extract halorhodopsin from its native membrane and compared the force-distance profiles with those of its cousin bacteriorhodopsin. The adhesive interhelical contacts are both weak and spatially diffuse, so that it is the sum total of them and not just a few residues that lend strength to the functional structure. The unfolding profiles also show, within one of the transmembrane helices in halorhodopsin, a hinge (defined by an alanine-tryptophan pairing) that demarcates two separably movable segments of the helix. — GJC

Structure 13, 235 (2005).

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