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Mark Yeager, M.D., Ph.D.

Professor Adjunct
Department of Molecular Medicine
California Campus
Laboratory Website
Scripps VIVO Scientific Profile
yeager@scripps.edu
(858) 784-8584

Research Focus

Structure of Supramolecular Assemblies: Membrane Proteins and Viruses

The ultimate goal of our studies is to gain a deeper understanding of the molecular basis for important human diseases such as sudden death, heart attacks and HIV infection that cause substantial mortality and suffering. The structural details revealed by our work may provide clues for the design of more effective and safer medicines.


At the basic science level, we are intrigued by biological questions at the interface between cell biology and structural biology: How do membrane proteins fold? How do membrane channels open and close? How are signals transmitted across a cellular membrane when an extracellular ligand binds to a membrane receptor? How do viruses attach and enter host cells, replicate and assemble infectious particles? To explore such problems, my colleagues and I use high resolution electron cryo-microscopy and computer image processing. By this approach, we can explore the molecular architecture of supramolecular assemblies such as membrane proteins and viruses. In electron cryo-microscopy, biological specimens are quick frozen in a physiological state to preserve their native structure and functional properties. A special advantage of this method is that dynamic states of functioning macromolecular assemblies can be captured (for example, open and closed states of membrane channels and viruses actively transcribing RNA). Three-dimensional density maps are obtained by digital image processing of the high resolution electron micrographs. The rich detail in the density maps demonstrates the power of this approach to reveal the structural organization of complex biological structures that can be related to the functional properties of such assemblies. Research projects underway include the structure analysis of membrane proteins involved with cell-to-cell communication (gap junctions), water transport (aquaporins), transmembrane signaling (integrins), and viral recognition (rotavirus NSP4), as well as viruses responsible for significant human disease (rotavirus, astrovirus, retroviruses).

Education

M.D. (Medicine), Yale University 1979
Ph.D. (Biology), Yale University, Department of Molecular Biophysics and Biochemistry 1978
B.S. (Chemistry), Carnegie Mellon University

Professional Experience

2014-2017 Professor Adjunct, Cell and Molecular Biology (CMB), The Scripps Research Institute
2013-2014 Professor of Molecular Physiology, Cell and Molecular Biology (CMB), The Scripps Research Institute
2001-2012 Professor of Molecular Physiology, Cell Biology, The Scripps Research Institute
2001-2012 Professor (Joint Appointment), Molecular Biology, The Scripps Research Institute
1994-2001 Associate Professor, Cell Biology, The Scripps Research Institute

Selected References

All Publications

For a complete list of publications: http://www.scripps.edu/yeager/publications.htm

Barbie K. Ganser, B.K., Cheng, A., Sundquist, W.I., and Yeager, M. Three-dimensional Structure of the M-MuLV CA Protein on a Lipid Monolayer: A General Model for Retroviral Capsid Assembly. EMBO J. (2003) [in press].

Adair, B.A. and Yeager, M. Three-dimensional Model of the Human Platelet Integrin aIIbb3 Based on Electron Cryo-Microscopy and X-ray Crystallography. Proc. Natl. Acad. Sci USA 99:14059-14064 (2002).

Tihova, M., Dryden, K.A., Bellamy, A.R., Greenberg, H.B., and Yeager, M. Localization of Membrane Permeabilization and Receptor Binding Sites on the VP4 Hemagglutinin of Rotavirus: Implications for Cell Entry. J. Mol. Biol. 314: 985-992 (2001).

Unger, V.M., Kumar, N.M., Gilula, N.B., and Yeager, M. Three-dimensional Structure of a Recombinant Gap Junction Membrane Channel. Science 283: 1176-1180 (1999).

Links

CIMBio