31
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session V Abstracts
Two Is Better than One: Molecular Mechanism of Sodium Coupling in the Betaine
Transporter BetP
Lucy R. Forrest,
Christine Ziegler
.
Max-Planck Institute of Biophysics, Frankfurt, Germany.
BetP is a Na
+
-coupled symporter that shares the highly conserved LeuT-like fold of two-inverted
structural repeats with other sequence unrelated secondary transporters, e.g., the medical
important neurotransmitter transporters. Recently, we have obtained atomic structures from BetP
in distinct conformational states, which elucidated the alternating access mechanism of BetP,
suggesting a common mechanistic principle in LeuT-like fold transporters. Our structural data in
combination with molecular dynamics simulations reveal key features of the formation of the
central betaine-binding site and the two sodium-binding sites. We suggest a sequential
Na
+
/substrate binding process in which the sodium ions are loosely associated with partially
formed sites in the outward-open state, in the absence of substrate. Subsequent binding of
substrate to the central binding site results in an improved coordination of the two ions. Whereas
one of the sodium ions seems to be responsible for closing the periplasmic pathway after
substrate binding, the other one controls the opening of the inward-facing pathway. Na
+
binding
and release are the key factors in guiding the alternating-access cycle in a pseudo symmetrical
fashion and therefore the different roles of the two sodium ions observed for BetP are of
particular interest for sodium-coupled secondary transporters.
