Biochemistry

Transport by the Numbers

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Science  19 Apr 2013:
Vol. 340, Issue 6130, pp. 250
DOI: 10.1126/science.340.6130.250-b

Twelve is a useful number when it comes to protein design. Why? Because divisibility by 2 and by 3 means that subunits or intraprotein domains can be assembled combinatorially while structural homologies insure stability. Madej et al. document a striking example of this flexibility in design by comparing the tertiary structures of two members of the major facilitator super-family (MFS) of secondary transporters. MFS transporters carry small molecules across the cell membrane, often in tandem with an ion; the movement of the small-molecule substrate, such as lactose or fucose, is driven by the electrochemical gradient of the ion, which is in turn established by active transporters. Both sugar permeases LacY and FucP consist of 12 transmembrane helices, and both of their secondary structures adhere to the canonical pattern of a quartet of three helix bundles. Biochemical analysis of mutant forms has identified the aromatic residues Trp151 and Phe308, respectively, as the platforms where the sugar substrates bind, but as is evident from their numbering, these functionally homologous residues are found in entirely different locations in the primary structure. Madej et al. discovered that LacY and FucP are inverted permutations of each other, with bundles A through D in LacY corresponding to bundles D through A in FucP.

Proc. Natl. Acad. Sci. U.S.A. 110, 10.1073/pnas.1303538110 (2013).

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