A conformational switch in a partially unwound helix selectively determines the pathway for substrate release from the carnitine/γ-butyrobetaine antiporter CaiT.

ABSTRACT: CaiT is a homotrimeric antiporter that exchanges l-carnitine (CRN) with γ-butyrobetaine (GBB) across the bacterial membrane. Three structures have been resolved to date for CaiT, all in the inward-facing state: CRN-bound (with four CRNs per subunit), GBB-bound (two GBBs per subunit), and apo. One of the reported binding sites is the counterpart of the primary site observed in structurally similar transporters. However, the mechanism and pathway(s) of CRN/GBB unbinding and translocation, or even the ability of the substrates to dislodge from the reported binding sites, are yet to be determined. To shed light on these issues, we performed a total of 1.3 μs of molecular dynamics simulations and examined the dynamics of substrate-bound CaiT structures under different conditions. We find that b

SUBMITTER: Zomot E 

PROVIDER: S-EPMC3442516 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature