Research Article: Structures of the substrate-binding protein YfeA in apo and zinc-reconstituted holo forms

Date Published: September 01, 2019

Publisher: International Union of Crystallography

Author(s): Christopher D. Radka, Shaunivan L. Labiuk, Lawrence J. DeLucas, Stephen G. Aller.


A cluster A-I substrate-binding protein reveals conformational changes, including an asymmetric rigid-body rotation of the flexible lobe, the reordering of a mobile helix and a spring-hammer mechanism.

Partial Text

Bacterial substrate-binding proteins (SBPs) belong to the widespread ABC superfamily and specifically have a role in sequestering various metabolites, including amino acids, nucleic acids, carbohydrates and metals (Scheepers et al., 2016 ▸). SBPs are thought to freely diffuse through the periplasm of Gram-negative bacteria, anchor to the cytoplasmic membrane of Gram-positive bacteria as a lipoprotein (Felder et al., 1999 ▸) or be covalently fused to membrane transporters (Gouridis et al., 2015 ▸). SBPs are highly abundant in the cell, and in some cases compose up to 40% of Gram-positive surface lipoproteins (Hutchings et al., 2009 ▸). SBPs and cognate ABC importers present attractive therapeutic targets because they are not found in humans, and infection studies have shown that disrupting these substrate-transfer mechanisms greatly attenuates virulence in animal models (Garmory & Titball, 2004 ▸; Paik et al., 2003 ▸; Janulczyk et al., 2003 ▸; Boyer et al., 2002 ▸; Brown et al., 2001 ▸; Fetherston et al., 1999 ▸; Bearden & Perry, 1999 ▸). SBPs have low primary amino-acid sequence identity, but share high tertiary-structural similarity when comparing SBPs that transfer similar substrates (Scheepers et al., 2016 ▸). Trends in the correlative relationships between structure and substrate have been organized into a cluster system that includes structural details unique to each SBP cluster (Berntsson et al., 2010 ▸). All SBPs follow an evolution­arily conserved c-clamp architecture containing α/β globular lobe domains connected by a backbone and interdomain β-strand hinges. In many cases, c-clamps bind substrates at their arch through a mechanism resembling a Venus flytrap, whereby the lobes of a substrate-free c-clamp freely rotate and then tightly clasp a substrate molecule, trapping it inside (Felder et al., 1999 ▸; Mao et al., 1982 ▸).




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