ISSN:
0006-3525
Keywords:
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Proline occurs frequently in transmembrane α-helices of transport and receptor proteins even though statistical surveys demonstrate the overwhelming preference of this residue for a non-α-helical, hydrophilic environment. As a result, membrane-buried proline has been proposed to be functionally important, with function arising from structural discontinuity or destabilization of the helix. Destabilization may occur by Promediated conformational transitions between discrete states, and may be manifested in membrane protein systems through reversible processes such as channel opening and closing or signal transduction. In this study, computer modeling of a model transmembrane α-helix, (Ala)8-Leu-Pro-Phe-(Ala)8, in a medium of low polarity (dielectric = 2), is used to examine the occurrence and energetic accessibility of Pro-mediated conformational interconversions. Leu ψ and χ1, Pro ψ and Phe φ and χ1 torsion angles were assigned random values so that a data base of 200 conformations for each of the cis and trans states was generated. The conformations were minimized and low-energy structures organized into families. This analysis demonstrated that the most populated lowest energy family is the Trans-I conformation, corresponding to proline in a kinked α-helix. Two additional trans structures, Trans-II and Trans-III, as well as a cis conformation, Cis-I, are also energetically competitive. Interconversions between the trans states could thus be mediated by changes at a single torsion angle, accompanied by minor local hydrogen-bonding rearrangements. This work substantiates that membrane-buried proline can provide the basis for conformational transitions between discrete α-helix-based structures in a nonpolar environment.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bip.360320416
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