protein folding in membranes, membrane protein targeting and assembly; membrane protein structure prediction, x-ray and neutron diffraction, structure of fluid bilayers, molecular dynamics simulations
U.S.P.H.S. Postdoctoral Fellowship, 1971; N.I.H. Research Career Development Award, 1976; Kaiser-Permanente Award for Excellence in Teaching (Basic Science), 1975; Alumnus of the University of California Management Institute, 1981; Kaiser-Permanente Award for Excellence in Teaching (Basic Science), 1992; President, Biophysical Society, 1996-1997; Biophysical Society Distinguished Service Award, 1999; Athalie Clarke Research Achievement Award, UCI College of Medicine, 2000; Biophysical Society Fellow, 2002; Ph.D honoris causa, Stockholm University, 2008; Biophysical Society Avanti Award in Lipids, 2009; Matrone Distinguished Lecture in Biochemistry, North Carolina State University, 2010; Cátedra de Investigación Científica, Autonomous University of San Luis Potosí, Mexico 2010; Frederic M. Richards Lecture, Yale, 2010; O'Malley Lectures in Chemical Biology, Boston College, 2011; Protein Society Carl Brändén Award, 2014
Served to the rank of captain in US Army, 1969-1971
USPH postdoctoral fellow, Dept. of Biochemistry, University of Virginia with Prof. T. E. Thompson, 1971-1972
Asst. Professor, UC Irvine, 1972
Professor, UCI Irvine, 1979
The prediction of 3D protein structure from sequence requires an understanding of the basic thermodynamic and structural principles of protein folding. My laboratory is dedicated to uncovering these principles for membrane proteins through studies of the interactions of polypeptides with fluid lipid bilayers. We are doing work in five broad areas: (1) Structural studies of fluid bilayers using x-ray and neutron diffraction, (2) structural determinations of the location of peptides in bilayers and their effects on bilayer structure, (3) physicochemical studies of peptide and protein interactions with lipid bilayers, (4) molecular dynamics simulations of membrane proteins, (5) translocon-assisted folding of membrane proteins, and (5) the development of web-based structure prediction tools. The basic strategy of the physicochemical measurements is to synthesize host/guest peptides for the systematic examination of the bilayer interactions of the guest amino acid in the host peptide. The structure prediction methods are built upon on hydropathy plot methods and the global statistics of protein sequences. The statistical studies provide insights to the statistical limits of structure prediction and to the early evolution of proteins.
Jacobs, R. E. and S. H. White. 1989. The nature of the hydrophobic binding of small peptides at the bilayer interface: Implications for the insertion of transbilayer helices. Biochemistry 28:3421.
Wiener, M. C. and S. H. White. 1992. The structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement using x-ray and neutron data. III. The complete structure. Biophys. J. 61:434.
Wimley, W. C.and S. H. White. 1996. Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nature Struct. Biol. 3:842-848
White, S. H. and W. C. Wimley. (1999). Membrane protein folding and stability: Physical principles. Annu. Rev. Biophys. Biomol. Struct. 28:319-365. (review article)
Ladokhin, A. S. and White, S. H. (1999). Folding of amphipathic a-helices on membranes: Energetics of helix formation by melittin. J. Mol. Biol. 285:1363-1369.
Hristova, K., Wimley, W. C., Mishra, V. K, Anantharamiah, G. M., Segrest, J. P., and White, S. H. (1999). An amphipathic a-helix at a membrane interface: A structural study using a novel x-ray diffraction method. J. Mol. Biol. 290:99-117.
Hristova, K., Dempsey, C. E., and White, S. H. (2001). Structure and lipid perturbations of melittin in the membrane interface. Biophys. J. 80:801-811.
Ladokhin, A. S. and White, S. H. (2001). Protein chemistry at the membrane interface: Non-additivity of electrostatic and hydrophobic interactions. J. Mol. Biol. 309:543–552.
Jayasinghe, S., Hristova, K., and White, S. H. (2001). Energetics, stability, and prediction of transmembrane helices. J. Mol. Biol. 312:927–934.
Wimley, W. C. and White, S. H. (2004). Reversible unfolding of ß-sheets in membranes: A calorimetric study. J. Mol. Biol. 342:703-711.
Castro-Román, F., Benz, R. W., Tobias, D. J., and White, S. H. (2005). Experimental validation of molecular dynamics simulations of lipid bilayers: A new approach. Biophysical Journal 88:805–817.
Hessa, T., Kim, H., Bihlmaier, K., Lundin, C., Nilsson, IM, White, S. H., and von Heijne, G. (2005). Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature 433:377–381
Hessa T, Meindl-Beinker NM, Bernsel A, Kim H, Sato Y, Lerch-Bader M, Nilsson I, White SH, & von Heijne G (2007). Molecular code for transmembrane-helix recognition by the Sec61 translocon. Nature 450:1026-1030.
White, S. H. and von Heijne, G. (2005). Transmembrane helices before, during, and after insertion. Current Opinion in Structural Biology 15:378-386. (Review)
Krepkiy D, Mihailescu M, Freites JA, Schow EV, Worcester DL, Gawrisch K, Tobias DJ, White SH, & Swartz KJ (2009). Structure and hydration of membranes embedded with voltage-sensing domains. Nature 462:473-479.
Öjemalm K, Higuchi T, Jiang Y, Langel U, Nilsson I, White SH, Suga H, & von Heijne G (2011). Apolar surface area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum. Proc Natl Acad Sci USA 108:E359-364
Ulmschneider MB, Ulmschneider JP, Schiller N, Wallace BA, von Heijne G, & White SH (2014). Spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion. Nature Comms 5:4863.
Lindner E & White SH (2014). Topology, dimerization, and stability of the single-span membrane protein CadC. J Mol Biol 426:2942-2957.
Cymer F, von Heijne G, & White SH (2015). Mechanisms of integral membrane protein insertion and folding. J Mol Biol 427:999-1022. (review)
Capponi S, Heyden M, Bondar AN, Tobias DJ, & White SH (2015). Anomalous behavior of water inside the SecY translocon. Proc Natl Acad Sci USA 112:9016-9021.
Membrane protein folding and assembly (RO1 GM74637)
American Crystallographic Association
American Society for Biochemistry and Molecular Biology
Society of General Physiologists
American Physical Society
American Chemical Society
Dept. of Physiology and Biophysics, UCI 1977—1989
Structural Biology and Molecular Biophysics
Program in Macromolecular Structure