Assistant Scientist, Vollum Institute
Matt Whorton graduated from Duke University in 2001 with a B.S. in Biology, and went on to obtain a Ph.D. in Pharmacology from the University of Michigan in 2008. He then did postdoctoral research at Rockefeller University before starting as an assistant scientist at the Vollum Institute in 2013.
Summary of current research
We are interested in understanding detailed mechanisms of how membrane proteins function. For instance, how is the opening and activity of ion channels, transporters, and receptors regulated by ligands and other proteins? How do ion channels and transporters selectively allow some ions and substrates through but not others? How do membrane-embedded enzymes catalyze their reactions, and why do they need to be at the membrane to do so?
Our general approach to answering these fundamental questions is through electrophysiological, biochemical, and biophysical functional studies, coupled with determining high-resolution structures of these proteins using X-ray crystallography.
Why are we interested in these questions? Cells have developed many ways to get nutrients, ions, and signaling information across the barrier of the lipid membrane. This places membrane proteins as central players in many physiological processes and makes them important drug targets. Understanding detailed mechanisms of how these proteins work is crucial for understanding how their function is related to disease states, and how this knowledge can be used to design new or more effective drugs.
Ahuja S, Whorton MR. (2019) Structural basis for mammalian nucleotide sugar transport. Elife 8:e45221.
Martin GM, Yoshioka C, Rex EA, Fay JF, Xie Q, Whorton MR, Chen JZ, Shyng SL. (2017) Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating. Elife 6:e24149.
Whorton M. (2014) Structural biology: Calcium-activated proteins visualized. (News & Views) Nature 516:176-178.
Wang W, Whorton MR, MacKinnon R. (2014) Quantitative analysis of mammalian GIRK2 channel regulation by G proteins, the signaling lipid PIP2 and Na+ in a reconstituted system. Elife 3:e03671.
Whorton MR, MacKinnon R. (2013) X-ray structure of the mammalian GIRK2-Gβγ G protein complex. Nature 498:190-197.
Whorton MR, MacKinnon R. (2011) Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G Proteins, PIP2, and sodium. Cell 147:199-208.
Whorton MR, Jastrzebska B, Park PSH, Fotiadis D, Engel A, Palczewski K, Sunahara RK. (2008) Efficient coupling of transducin to monomeric rhodopsin in a phospholipid bilayer. J. Biol. Chem. 283:4387-4394.
Whorton MR, Bokoch MP, Rasmussen SGF, Huang B, Zare RN, Kobilka B, Sunahara RK. (2007) A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein. Proc. Natl. Acad. Sci. USA 104:7682-7687.