Membrane Protein Structure and Function Unit - Division of Intramural Research
Reinhard Grisshammer, Ph.D., Investigator
Dr. Grisshammer received his university degree in Biology and Chemistry in 1985 from the Ludwig-Maximilians-University in Munich, Germany. In 1990, he received his Ph.D. degree from the Johann-Wolfgang Goethe University in Frankfurt, Germany, where he worked with Hartmut Michel at the Max-Planck-Institute of Biophysics studying the c-type subunit of the photosynthetic reaction center of Rhodopseudomonas viridis. Dr. Grisshammer did post-doctoral work with Richard Henderson at the Medical Research Council Laboratory of Molecular Biology, Cambridge, England, where he focused on structural work on G-protein-coupled receptors. Dr. Grisshammer joined NIDDK in 2001 as staff scientist, and NINDS in 2006 as investigator. His laboratory is using a combination of structural and functional approaches to answer mechanistic questions regarding G-protein-coupled receptors.
Our research focuses on the structure determination of integral membrane proteins, with emphasis on seven-helix G-protein-coupled receptors. Relevant techniques encompass heterologous overexpression including development of new strategies for improved yields, purification at large scale in functional form, biochemical and pharmacological characterization, and crystallization. Our aim is to obtain well-ordered crystals to solve structures at high resolution.
We also investigate the signaling properties of GPCRs by using functional assays in combination with the nanodisc technology, exploring the influence of lipid and the aggregational state of receptors on the interaction with G-proteins, kinases and arrestin molecules.
Selected Recent Publications
Why we need many more GPCR structures, Expert Review of Proteomics, 2013, vol. 10, pp. 1-3.
Shibata Y, Gvozdenovic-Jeremic J, Love J, Kloss B, White JF, Grisshammer R, Tate CG
Optimising the combination of thermostabilising mutations in the neurotensin receptor for structure determination, Biochim Biophys Acta Biomembranes, 2013, vol. 1828, pp. 1293-1301.
Xiao S, White JF, Betenbaugh MJ, Grisshammer R, Shiloach J
Transient and stable expression of the neurotensin receptor NTS1: A comparison of the baculovirus-insect cell and the T-REx-293 expression systems, PlosOne, 2013, vol. 8, pp. e63679.
Inagaki S, Ghirlando R, Grisshammer R
Biophysical characterization of membrane proteins in nanodiscs, Methods, 2013, vol. 59, pp. 287-300. Full Text/Abstract
Inagaki S, Ghirlando R, White JF, Gvozdenovic-Jeremic J, Northup JK, Grisshammer R
Modulation of the interaction between neurotensin receptor NTS1 and Gq protein by lipid, J Mol Biol, 2012, vol. 417, pp. 95-111.
White JF, Noinaj N, Shibata Y, Love J, Kloss B, Xu F, Gvozdenovic-Jeremic J, Shah P, Shiloach J, Tate CG, Grisshammer R
Structure of the agonist-bound neurotensin receptor, Nature, 2012, vol. 490, pp. 508-513.
White JF, Grisshammer R
Stability of the neurotensin receptor NTS1 free in detergent solution and immobilized to affinity resin, PLoS One, 2010, vol. 5, pp. e12579.
Purification of recombinant G-protein-coupled receptors, Methods in Enzymology, Guide to Protein Purification, Second Edition, 2009, vol. 463, pp. 631-645.
Selected Earlier Publications