Erik Procko

318G Roger Adams Laboratory
Office: 217-300-1454

Mail to:
419 RAL Box 4B
600 South Mathews Ave.
Urbana, IL 61801

Erik Procko

Assistant Professor, Department of Biochemistry
B.Sc. 2002 University of Adelaide, Australia
B.Sc.(Hons) 2003 University of Adelaide, Australia
Ph.D. 2008 Harvard University, Boston
Postdoc. 2009-2014 University of Washington, Seattle

Molecular Mechanisms of G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) typically interact with their ligands at binding sites within a membrane-spanning region. GPCRs are intrinsically flexible proteins, and these ligand interactions within the transmembrane region stabilize distinct conformations that impact downstream signaling. However, some GPCRs defy the general stereotype, and instead have large extracellular domains that bind ligands far from the membrane. How ligand interactions way out from the cell surface can still stabilize the active receptor conformation at the membrane is unclear. These trend-breaking GPCRs include many important and interesting chemosensory receptors, including those for sweet and umami tastes, pheromones, and the major excitatory and inhibitory neurotransmitters. Of particular focus in the lab is the sweet receptor. Not only will an understanding of this receptor have potential industrial applications for the sweetener market, but also several high-affinity sweet plant proteins are available as excellent biochemical tools.

What is the molecular basis for the recognition of sweet substances? How can diverse sweet substances, ranging from small sugars and artificial sweeteners to large proteins, all induce an active conformation of the sweet receptor? Can new sweet substances, in particular peptides and small proteins, be rationally designed? What conformational changes occur in a large multi-domain and multi-chain GPCR?

The Procko lab will bring new methods to study the sweet taste receptor and homologous receptors. We are particularly excited to be developing methods for the deep mutational scanning and directed evolution of transmembrane proteins in mammalian cells. Using simple chemokine receptors to develop our protocols, we are now able to combine in vitro evolution with deep sequencing to characterize the phenotypes of thousands of receptor mutants at an unprecedented scale. This has led to additional projects using deep mutational scanning to investigate interactions between chemokine receptors and HIV-1 envelope proteins, and the mechanisms of neuronal transporters. Together with other biochemical, computational and structure determination methods, the molecular mechanism of this GPCR family will be explored with anticipated broader implications for GPCR signaling.

Research Areas

Representative Publications

Procko E,* Berguig GY,* et al. (2014) A computationally designed inhibitor of an Epstein-Barr viral BCL-2 protein induces apoptosis in infected cells. Cell 157(7):1644-56.

Procko E, Hedman R, Hamilton K, Seetharaman J, Fleishman SJ, Su M, Aramini J, Kornhaber G, Hunt JF, Tong L, Montelione GT, Baker D. (2013) Computational design of a protein-based enzyme inhibitor. J Mol Biol 425(18):3563-75.

Geibel S,* Procko E,* Hultgren SJ, Baker D, Waksman G. (2013) Structural and energetic basis of folded-protein transport by the FimD usher. Nature 496(7444):243-6.

Lau SY, Procko E, Gaudet R. (2012) Distinct properties of Ca2+-calmodulin binding to N- and C-terminal regulatory regions of the TRPV1 channel. J Gen Physiol 140(5):541-55.

Inada H, Procko E, Sotomayor M, Gaudet R. (2012) Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel. Biochemistry 51(31):6195-206.

Procko E, Gaudet R. (2009) Antigen processing and presentation: TAPping into ABC transporters. Curr Opin Immunol 21(1):84-91.

Procko E, O’Mara ML, Bennett WFD, Tieleman DP, Gaudet R. (2009) The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter. FASEB J 23(5):1287-302.

Procko E, Gaudet R. (2008) Functionally important interactions between the nucleotide-binding domains of an antigenic peptide transporter. Biochemistry 47(21):5699-708.

Lishko PV,* Procko E,* Jin X,* Phelps CB, Gaudet R. (2007) The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron 54(6):905-18.

Procko E, Ferrin-O'Connell I, Ng SL, Gaudet R. (2006) Distinct structural and functional properties of the ATPase sites in an asymmetric ABC transporter. Mol Cell 24(1):51-62.

Complete Publications List (PubMed)