Research Highlights

Prof. dr. Dirk Slotboom

Lipid bilayer-steered transport of vitamins

We have derived a model for chemo-mechanical coupling during transport of vitamins by a bacterial transporter:

• The energy harnessed from ATP binding and hydrolysis is used to reset the substrate-free transporter (state 1 to state 2 in the figure). ATP binding charges the coupling helices like ‘springs’ in order to expel the substrate translocating domain (S-component) from the motor complex (red, orange and blue subunits) into the bilayer.

• ATP hydrolysis is utilized to release the tension of the ‘springs’ and modulates the membrane morphology in order to prepare for S-component docking and binding (state 2 to state 3).

• Once a substrate is bound to the S-component (state 3 to state 4), it can topple over in the bilayer and associate motor complex, alike a thermal ratchet (state 4 to state 1).

The toppling and thermal ratchet mechanism is unprecedented and is a manifestation of the diversity of transport solutions adopted by the superfamily ATP-binding cassette transporters. The fundamental structural and mechanistic insights from this work may have wider implications, since exchange of S-components from different organisms upon horizontal gene transfer may contribute to the ability of bacteria to rapidly acquire new metabolic functionality, or even antibiotic resistance.

Reference:

Thangaratnarajah C, Nijland M, Borges-Araujo L, Jeucken A, Rheinberger J, Marrink SJ, Souza PCT, Paulino C & Slotboom D (2023) Expulsion mechanism of the substrate-translocating subunit in ECF transporters. Nature Communications 14: 4484.