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Pawel A. Penczek
The University of Texas - Houston Medical SchoolDepartment: Biochemistry and Molecular BiologyAddress: 6431 Fannin, MSB 6.128 Houston, TX 77030 Phone: (713) 500-5416 Fax: (713) 500-0652 Email: Pawel.A.Penczek@uth.tmc.edu Web: |
Education
M.S., Medical Physics, Warsaw University (1979)
Ph.D., Physics, Warsaw University (1988)
Postdoc: Wadsworth Center, Albany, NY (Prof. J. Frank)
Honors
Research Topic
Structural Determinatin of Proteins and Molecular Assemblies
Research Description
We are interested in the determination of three-dimensional structures of large macromolecular complexes with low or non-existing symmetry in single-particle form using stain and cryo-electron microscopy (cryo-EM) and computer image processing techniques.
One area of focus is determination of the structure of a newly identified protein called HRS (hepatocyte growth factor regulated tyrosine kinase substrate). HRS is phosphorylated by various kinases in response to a variety of growth factors and is expressed in the cytoplasm of all cells. In addition, HRS was also implicated in exocytosis of synaptic vesicles. The main interest is in its regulatory functions. The determination by cryo-EM of tertiary structure of HRS together with knowledge of its amino acid sequence will lead to localization of functional domains of this protein. In order to bridge a gap between X-ray crystallographic results and the cryo-EM structure, a major effort will be devoted to the improvement of the resolution of cryo-EM results to a near-atomic level.
Our main area of interest is high-resolution cryo-EM and the development of efficient and largely automatic tools for single particle analysis and three-dimensional reconstruction. Due to a very low Signal-To-Noise Ratio of EM data, there is a necessity to collect and merge large numbers (in excess of 100,000) of individual particle images. Thus, in our approach we will focus on automatic particle picking utilities that should be able to cope with a large number of micrographs under various noise conditions.
Unconstrained by crystal packing, the molecule in a single particle specimen can be thought to exhibit the entire range of native conformations. The ability to find the structure of each conformer is one of the most important potential assets of 3D cryo-EM of single particles. On the other hand, the realization of high resolution for each of these conformers poses daunting problems of data collection and processing, considering the statistical requirements stated before. Therefore, we are also interested in the development of efficient and robust computational methods of resolution refinement in the presence of multiple conformational or binding states.
Selected Publications
- Penczek, P.A. (2002). Three-dimensional spectral signal-to-noise ratio for a class of reconstruction algorithms. J. Struct. Biol. 138: 34-46.
- Joyeux, L. and Penczek, P.A. (2002). Efficiency of 2D alignment methods. Ultramicroscopy 92: 33-46.
- Spahn, Ch.M.T., Kieft, J.S., Grassucci, R.A., Penczek, P.A., Zhou, K., Doudna, J.A. and Frank, J. (2001). Hepatitis C virus IRES RNA induced changes in the conformation of the 40S subunit. Science 291: 1959-1962.
- Spahn Ch.M. T., J.S. Kieft, R.A. Grassucci, P.A. Penczek, K. Zhou, J.A. Doudna, J. Frank. (2001). Hepatitis C virus IRES RNA induced changes in the conformation of the 40S subunit. Science 291: 1959-1962.
- Spahn, Ch.M.T, Penczek, P.A., Leith, A., Frank, J. (2000). A method for differentiating proteins from nucleic acids in intermediate-resolution density maps: cryo-electron microscopy defines the quaternary structure of the Escherichia coli 70S ribosome. Structure 8: 937-948.
Lab Members
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Last edited on: December 17, 2003