Cylindrical Channels from Concave Helices

The crystal structure of the bacterial mechanosensitive channel (MscS) reveals a striking molecular architecture with seven-fold symmetry and a central channel formed from tightly packed α-helices that partially span the membrane “(Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel,” R. D. Bass et al. , Research Articles, 22 Nov., p. [1582][1]). We were struck by the fact that the α-helices of the central channel are nearly straight; earlier, we had found α-helices in an analogous assembly that curved and untwisted in order to lie on a cylindrical surface ([1][2]). Here, we present a simple model to explain how MscS can form cylindrical channels from straight helices. In the wider family of channels related to MscS, there is absolute conservation of a pattern of glycines (GxxGxxxG). The MscS crystal structure shows that these glycines lie in a group on one side of each helix and form the packing interface with the next helix. The contacting residues of the neighboring helix are alanines (A), and the molecular symmetry of the channel enforces the sequence pattern AxxGAxGxAxG. A simplified, triangulated model of the helical interface between neighboring helices can be made by linking points representing the Cβ atoms or, in the case of the glycines, the Cα atoms. This is shown in the left panel of the figure. In the right panel is the triangulated representation using only the Cα positions; this shows that each helix is straight and fairly uniform (in fact, they are untwisted; i.e., they have a helical repeat of roughly 3.5 residues per turn). In contrast, the Cβ/Cα helix has an apparent concavity on account of the three glycines, and this enables the two straight helices to fit snugly in a right-twisted arrangement. ![Figure][3] Triangulated representations of the MscS α-helix. (Left) Cβ/Cα atoms. (Right) Cα atoms only. The same pattern of glycines (GxxGxxxG) is absolutely conserved in the family of bacterial membrane proteins that are involved in proton-dependent transmembrane transport (TolQ, ExbB) and flagellar rotation (MotA). We suggest that these will probably also form tubular, trans-membrane assemblies with a right-twisted arrangement. However, the residues flanking the conserved glycines are generally β-branched in these proteins and are rarely alanine; hence, the details of packing and stoichiometry are likely to differ from those observed in the MscS architecture. 1. [↵][4]1. C. R. Calladine, 2. A. Sharff, 3. B. Luisi , J. Mol. Biol. 305, 603 (2001). [OpenUrl][5][CrossRef][6][PubMed][7][Web of Science][8] [1]: /lookup/doi/10.1126/science.1077945 [2]: #ref-1 [3]: pending:yes [4]: #xref-ref-1-1 View reference 1 in text [5]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2Bmolecular%2Bbiology%26rft.stitle%253DJ%2BMol%2BBiol%26rft.aulast%253DCalladine%26rft.auinit1%253DC.%2BR.%26rft.volume%253D305%26rft.issue%253D3%26rft.spage%253D603%26rft.epage%253D618%26rft.atitle%253DHow%2Bto%2Buntwist%2Ban%2Balpha-helix%253A%2Bstructural%2Bprinciples%2Bof%2Ban%2Balpha-helical%2Bbarrel.%26rft_id%253Dinfo%253Adoi%252F10.1006%252Fjmbi.2000.4320%26rft_id%253Dinfo%253Apmid%252F11152616%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [6]: /lookup/external-ref?access_num=10.1006/jmbi.2000.4320&link_type=DOI [7]: /lookup/external-ref?access_num=11152616&link_type=MED&atom=%2Fsci%2F299%2F5607%2F661.atom [8]: /lookup/external-ref?access_num=000167760800020&link_type=ISI