Irina I. Serysheva, Ph.D.

National Center for Macromolecular Imaging

Verna and Marrs McLean Department of Biochemistry & Molecular Biology

Baylor College of Medicine, One Baylor Plaza, Houston TX 77030, U.S.A.

Tel. : (713) 798-6989 ;
(713) 798-6636 (EM lab)

Fax : (713) 798-3475

irinas@bcm.tmc.edu

curriculum vitae (in NIH format)

my family

Research interests

Intracellular Ca²⁺ signalling is one of the most ancient second messenger pathways in cell which is of vital importance in such diverse physiological functions as muscle contraction, neurotrasmitter release, fertilization, hormone secretion, gene transcription, metabolic regulation and apoptosis. It is based on ability of cells to maintain low levels of Ca²⁺ under resting conditions and to create a rapid and transient increase of Ca²⁺ upon the stimulated entry of Ca²⁺ ions through the plasma membrane. Key elements for this pathway are Ca²⁺ pumps and C²⁺ channels on plasma membrane and on internal organelles. The goal of our research is to understand molecular mechanisms underlying ion transport into and out of the cell across the surface membrane, or between different intracellular compartments through structure-function studies of membrane proteins and the macromolecular assemblies they form.

In our studies we use electron cryomicroscopy and computer reconstruction techniques in conjunction with biochemical, electro physiological and molecular biological techniques. To date, electron cryomicroscopy is proving to be one of the most important structural approaches in cell biological studies. We use "single particle" approach which relies on analysis of large number of electron images of isolated unordered macromolecules preserved in a layer of vitreous ice.

Recent focus has been on structural analysis of integral membrane Ca²⁺ release channels that mediate ligand-gated release of Ca²⁺ from intracelluar stores: the inositol 1,4,5-trisphosphate-sensitive Ca²⁺ release channel (InsP₃R), localized in the endoplasmic reticulum, and the ryanodine-sensitive Ca²⁺ release channel (ryanodine receptor, RyR), the primary Ca²⁺ channel in muscle cells. Both channels are large homotetrameric protein complexes with a molecular mass of ~2.3 MDa for RyRs and 1.2 MDa for InsP₃Rs. Large size and dynamic properties of these ion channels render their structural determination by standard structural techniques like X-ray crystallography or NMR spectroscopy, while electron cryomicroscopy is able to tackle both, large macromolecular assemblies as well as molecules in different functional states.

Another avenue of our research if the L-type voltage-gated Ca²⁺ channel (~430 kDa) is a hetero-oligomeric protein complex composed of five subunits. Even though the resolution of our current structures is limited to 20-30 Å, the low-resolution information is often useful for advancing the understanding of the system particularly when the structural studies are carried out along with biochemical labeling or modification. Our ultimate goal is extending these studies to higher resolution (8-10 Å) in order to build an anatomic model of these molecular complexes at well-defined functional states.

Selected Publications:

Ludtke, S. J., Serysheva, I. I., Hamilton, S. L. & W. Chiu (2005). The pore structure of the closed RyR1 channel. Structure, 13: 1203-1211.

Serysheva, I. I., Hamilton, S. L., Wah, C. & S. J. Ludtke (2005). Structure of Ca²⁺ release channel at 14 Å resolution. J. Mol. Biol., 345: 427-431.

Serysheva, I. I., Bare, D. J., Ludtke, S. L., Kettlun, C. S., Wah, C. & G. A. Mignery (2003). Structure of the Type 1 Inositol 1,4,5-Trisphosphate Receptor Revealed by Electron Cryomicroscopy. J. Biol. Chem., 278: 21319-21322.

Baker, M. L., Serysheva, I. I., Sencer, S., Wu, Y., Ludtke, S. L., Jiang, W., Hamilton, S. L. & W. Chiu (2002). The skeletal muscle Ca²⁺ release channel has an oxidoreductase-like domain. PNAS, 99: 12155-12160.

Serysheva, I. I., Ludtke, S. L., Baker, M. R., Chiu, W & S. L. Hamilton (2002). Structure of the voltage-gated L-type Ca²⁺ channel by electron cryomicroscopy. PNAS, 99: 10370-10375.

Pate, P., Mochca-Morales, J., Wu, Y., Zhang, J. Z., Rodney, G. G., Serysheva, I. I., Williams, B. Y. W., Anderson, M. E. & S. L. Hamilton (2000). Determinants for Calmodulin Binding on Voltage-dependent Ca²⁺ Channels. J. Biol. Chem., 275: 39786-39792.

Serysheva,I.I., Schatz, M., van Heel, M., Chiu, W. & Hamilton, S.L. (1999). Structure of the Skeletal muscle Calcium Release Channel Activated with Ca²⁺and AMP-PCP. Biophys. Journal, 77: 1936 -1944.

Orlova, E.V., Serysheva, I.I., van Heel, M., Hamilton, S.L. & Chiu, W. (1996). Two structural configurations of the skeletal muscle calcium release channel. Nature Struct. Biology, 3:547-552.

Serysheva, I.I., Orlova, E.V., Chiu, W., Sherman, M.B., Hamilton, S.L. & van Heel, M. (1995). Electron cryomicroscopy and angular reconstitution used to visualize the skeletal muscle calcium release channel. Nature Struct. Biology, 2:18-24.

Serysheva, I.I., Hamilton, S.L. (1998). Ryanodine Binding Sites on the Sarcoplasmic Reticulum Ca²⁺ Release Channel, pp. 95 - 110 in Ryanodine Receptors, ed. R. Sitsapesan and A. Williams, J. B. Lippincott Co., Philadelphia, P.A..

Orlova, E.V., Serysheva, I.I., Hamilton, S.L., Chiu, W. & M. van Heel (1998). The Skeletal Muscle Calcium-Release Channel visualized by Electron Cryomicroscopy and Angular Reconstitution, pp. 23 - 46 in Ryanodine Receptors, ed. R. Sitsapesan and A. Williams, J. B. Lippincott Co., Philadelphia, P.A..

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Last update: October 3, 2003
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