... understanding life in molecular detail

Dr Stan Burgess

Molecular motors, dynein, myosin, cytoskeleton, electron microscopy

I am interested in how the motor proteins of the eukaryotic cytoskeleton generate force and movement. Electron microscopy is my preferred approach to investigate the structure of the motor dynein on its microtubule track and of the motor myosin on its actin track.

Current major projects include:
  • Determining conformational changes within a single motor of dynein
  • Investigating the structure of the entire dynein motor supercomplex
  • Discovering how the dimeric dynein motor walks along its microtubule
  • Investigating dyneinâ??s regulatory binding partners, principally dyna

Eukaryotic cells use molecular motors, running along cytoskeletal tracks, to deliver and hold in place a bewildering diversity of cellular cargoes and components, essential for life. This is what allows eukaryotic cells to become both large (a single human motor neuron is up to a metre long) and complex. There are three types of cytoskeletal molecular motors: kinesins and dyneins which run on microtubule tracks, and myosins which run on tracks made of actin filaments. Numerous isoforms of these motors exist, some evolved for specialized functions, others more general purpose. These motors provide eh forces and movement that produce one of the most defining characteristics of life- directed movement. This includes not only moving components around within the cell, but also organizing its division into two cells, powering cell crawling, cell swimming (cilia and flagella) and even macroscopic movements of tissues (the beating of the heart) and all our muscular activities.

My research has focussed on how proteins from the myosin and dynein superfamilies of motors produce movement. Conformational changes within the motors, driven by the binding and hydrolysis of ATP, causes two major events in the motor: a change in binding affinity for its track and the movement of a mechanical element to drive motion in a particular direction while the motor is tightly bound to its track. Structural studies using NMR, X-ray crystallography and electron microscopy have all contributed to an increasingly deeper understanding of the conformational changes occurring within the motors. But to understand the motor fully it must be studied while bound to, and in some cases walking along, its molecular track. For this, electron microscopy is the only structural technique that is capable of the job. Current methods in electron microscopy allow the application of computational image analysis (single particle image processing) to determine not only the 3-dimensional structure of a protein complex from thousands of images of individual molecules, but also to study their flexibility- an important feature of motors working at this physical scale.

The figure shows one example- a dynein-c motor (one of the several dyneins) found in ordered arrays within cilia and flagella, in this case the single-celled alga called Chlamydomonas reinhardtii (upper panel). Dynein motor action here drives sliding between groups of microtubules that is somehow harnessed into propagated bending, though the details remain mysterious. We discovered that isolated dynein-c undergoes a large conformational change (so-called linker remodelling) that alters the relative position of its track binding stalk (yellow) with respect to its cargo-carrying tail. We also found that the tail is flexible (lower panel), which has implications for this motor’s ability to reach along its track to the next available binding site.                                                                                     

Detailed research programme                  Close ▲

Selected Publications

  1. Walker, M.L., Burgess, S.A., Sellers, J.R., Wang, F., Hammer III, J.A., Trinick, J. & Knight, P.J. (2000) Nature 405, 804-807. Two-headed binding of a processive myosin to F-actin.

  2. Burgess, S.A., Walker, M.L., Sakakibara, H., Knight, P.J. & Oiwa, K. (2003) Nature 421, 715-718. Dynein structure and power stroke.

  3. Burgess, S.A., Yu, S., Walker, M.L., Hawkins, R.J., Chalovich, J.M. & Knight, P.J. (2007). J. Mol. Biol. 372, 1165-1178. Structures of smooth muscle myosin and heavy meromyosin in the folded, shutdown state.

  4. Roberts, A.J., Numata, N., Walker, M.L., Kato, Y.S., Malkova, B., Kon, T., Ohkura, R., Arisaka, F., Knight, P.J., Sutoh, K. & Burgess, S.A. (2009). Cell 136, 485-495. AAA+ ring and linker swing mechanism in the dynein motor.