Mechanical Design of Translocating Motor Proteins

Abstract

Translocating motors generate force and move along a biofilament track to achieve diverse functions including gene transcription, translation, intracellular cargo transport, protein degradation, and muscle contraction. Advances in single molecule manipulation experiments, structural biology, and computational analysis are making it possible to consider common mechanical design principles of these diverse families of motors. Here, we propose a mechanical parts list that include track, energy conversion machinery, and moving parts. Energy is supplied not just by burning of a fuel molecule, but there are other sources or sinks of free energy, by binding and release of a fuel or products, or similarly between the motor and the track. Dynamic conformational changes of the motor domain can be regarded as controlling the flow of free energy to and from the surrounding heat reservoir. Multiple motor domains are organized in distinct ways to achieve motility under imposed physical constraints. Transcending amino acid sequence and structure, physically and functionally similar mechanical parts may have evolved as nature’s design strategy for these molecular engines.

Tagetitoxin Inhibits RNA Polymerase through Trapping of the Trigger Loop

“…RNAPs carry out a complex reiterative process of mechanochemical work, which requires a certain degree of conformational mobility of their subunits and/or domains, characteristic of all macromolecular motors (30). Range of motions associated with transcription varies greatly from small oscillations of a catalytic loop (31) to large scale ratcheting of the entire RNAP (32).…”

Microtubule shuttles on kinesin-coated glass micro-wire tracks

“…The motor protein kinesin 'walks' on the microtubule to carry out many vital functions in the cell, including intracellular transport and cell division (McIntosh, 2012;Hirokawa, 2009;Vale 2003). Kinesin uses adenosine triphosphate (ATP) as a fuel and its 8 nm step size corresponds to the size of the tubulin pitch forming the microtubule (Vale and Milligan, 2000;Hwang and Lang 2009). Due to their physiological importance, pharmaceutical targeting of microtubules and kinesin is under intensive study for diseases such as Alzheimer's disease and cancer (Zhou and Giannakakou, 2005;Craddock et al, 2012;Rath and Kozielski, 2012).…”

Microtubule guiding in a multi-walled carbon nanotube circuit

“…For example, the mechano-enzyme kinesin-1 (hereafter referred to as kinesin) converts chemical energy into mechanical work with a yield as high as 60 % (Hess et al 2004;Hwang and Lang 2009). Consuming one Adenosine Triphosphate (ATP) molecule per 16 nm step which results in a 8 nm displacement, kinesin is able to perform about 100 step/s, at a speed of 800 nm/s (Howard et al 1989).…”