|Structure and mechanism of the motor protein dynein||Group leader: Andrew Carter | MRC Laboratory of Molecular Biology, Cambridge|
How can the motor protein dynein transport so many different cargos? And what does the whole dynein look like at an atomic level? These are some of the research questions that Andrew Carter’s lab at the MRC LMB in Cambridge is working on.
Andrew Carter became interested in structural biology during his undergraduate studies in biochemistry at the University of Oxford, and moved on to do his PhD with Venki Ramakrishnan in Cambridge. Here, he was part of the team who solved the 30S ribosome structure, work that subsequently led to Ramakrishnan being awarded the Nobel Prize in Chemistry in 2009. After completing his PhD, Andrew moved to Ron Vale’s lab in San Francisco, California, where he started working on dynein.
Dynein is a motor protein that moves along microtubules, fuelled by ATP hydrolysis. It is, together with the protein complex dynactin, involved in many different processes, including intracellular transport, cell division, and organisation of the contents in eukaryotic cells. Cytoplasmic dynein is the largest and most complex of all the motor proteins – dynein itself has a mass of 1.4 MDa, and the dynein-dynactin complex is a 2.4 MDa machine. It is not surprising that elucidating its mechanism is a sizable task! In addition to dynein’s large size and complexity, its low abundance means that structural studies of dynein have been especially challenging and have remained a largely unexplored field. Andrew Carter is overcoming these experimental obstacles, using a variety of methods. The Carter lab used X-ray crystallography to explain how ATP hydrolysis allows the dynein motor to move along the microtubules. Later, they determined the structure of dynactin using cryo EM, enabling them to show how dynactin interacts with dynein. Recently, the Carter lab has also done single-molecule studies to investigate the force production of the dynein-dynactin complex. The running title of Andrew’s talk is “The 3.5Å cryo-EM structure of a fast dynein/dynactin complex”, and we are very much looking forward to what will no doubt be an interesting lecture!