Coupling of calcium and substrate binding through loop alignment in the outer-membrane transporter BtuB.

ABSTRACT: In Gram-negative bacteria, TonB-dependent outer-membrane transporters bind large, scarce organometallic substrates with high affinity preceding active transport. The cobalamin transporter BtuB requires the additional binding of two Ca(2+) ions before substrate binding can occur, but the underlying molecular mechanism is unknown. Using the crystallographic structures available for different bound states of BtuB, we have carried out extended molecular dynamics simulations of multiple functional states of BtuB to address the role of Ca(2+) in substrate recruitment. We find that Ca(2+) binding both stabilizes and repositions key extracellular loops of BtuB, optimizing interactions with the substrate. Interestingly, replacement by Mg(2+) abolishes this effect, in accordance with experiments. Us

SUBMITTER: Gumbart J 

PROVIDER: S-EPMC2775145 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature