Nano Science and Technology InstituteNano Science and Technology Institute
Nano Science and Technology Institute 2004 NSTI Nanotechnology Conference & Trade Show
Nanotech 2004
BioNano 2004
Program
Topics & Tracks
Sunday
Monday
Tuesday
Wednesday
Thursday
Index of Authors
Keynotes
Awards
Tutorials
Business & Investment
2004 Sub Sections
Sponsors
Exhibitors
Venue 2004
Proceedings
Organization
Press Room
Purchase CD/Proceedings
NSTI Events
Subscribe
Site Map
 
Nanotech Proceedings
Nanotechnology Proceedings
Supporting Organizations
Nanotech Supporting Organizations
Media Sponsors
Nanotech Media Sponsors
Event Contact
696 San Ramon Valley Blvd., Ste. 423
Danville, CA 94526
Ph: (925) 353-5004
Fx: (925) 886-8461
E-mail:
 
 

Membrane Proteins: Nanomachines with Optimized Structure and  Function

A. Engel
M.E. Müller Institute, University of Basel, CH

Keywords: membrane proteins, nanomachines, optimized structure, optimized function

Abstract:
Membrane proteins comprise more than 30% of the proteome of higher organisms. With characteristic dimensions of 5-10 nm they are membrane-embedded nanomachines that fulfill key functions such as signal transduction, energy conversion, solute transport and secretion. While the structure of more than 10'000 soluble proteins are solved, the number of membrane protein structures is smaller than 100. Since membrane proteins are involved in a wide range of diseases, and because a large majority of therapeutics is targeted to membrane proteins, knowledge of their structure is urgently required. 2D crystals of purified membrane proteins reconstituted in the presence of lipids provide a close to native environment and allow the structure and function of membrane proteins to be assessed. The surface structure of such membrane protein arrays can be determined in buffer solutions by atomic force microscopy (AFM) at a lateral resolution of 0.4 - 1 nm and a vertical resolution of 0.1 - 0.2 nm 1. In addition, single proteins can be addressed and unfolded, revealing the forces that dictate the protein's fold 2. The unique capability of the AFM to observe and manipulate single proteins in a physiological environment allows their function and dynamics to be directly monitored. Thus information about the surface structure of membrane proteins can be obtained by AFM from tightly packed, but disordered membranes. In contrast, electron microscopy relies on perfectly ordered 2D crystals, from which the 3D structure of a native membrane protein can be elucidated to a resolution of 0.3 nm by crystallographic averaging 3. Several types of membrane proteins have been studied by these methods. AFM was used to visualize voltage and pH dependent conformational changes of the bacterial channel OmpF 4. These changes suggest a mechanism, which protect the cells from drastic changes of the environment. The smallest turbines that convert the electrochemical potential produced by sunlight into mechanical energy, have been depicted by AFM, showing the subunits of the rotors 5. Rhodopsin, the G protein-coupled receptor responsible for vision was shown to exist in a dimeric and higher oligomeric state in the native murine disk membrane 6. Our results obtained by AFM support a wealth of biochemical and pharmacological data on the dimerization of GPCRs, which represent the most important class of drug targets. Electron crystallography was used to determine the structure of aquaporin-1 7 the highly specific water channel that filters more than 150 liters of pro-urine in our body every day 8. X-ray crystallography has subsequently confirmed the structure found by electron crystallography 9. These atomic structures facilitated molecular dynamic simulations to elucidate the permeation of water and exclusion of protons for both channels 10; 11. The wealth of information acquired over the last few years suggest a quantum leap in the understanding of membrane proteins in the near future. 1. Engel, A. & Muller, D. J. (2000). Nat Struct Biol 7, 715-8. 2. Oesterhelt, F., Oesterhelt, D., Pfeiffer, M., Engel, A., Gaub, H. E. & Muller, D. J. (2000). Science 288, 143-6. 3. Fujiyoshi, Y. (1998). Adv Biophys 35, 25-80. 4. Müller, D. J. & Engel, A. (1999). J Mol Biol 285, 1347-51. 5. Seelert, H., Poetsch, A., Dencher, N. A., Engel, A., Stahlberg, H. & Muller, D. J. (2000). Nature 405, 418-9. 6. Fotiadis, D., Liang, Y., Filipek, S., Saperstein, D. A., Engel, A. & Palczewski, K. (2003). Nature 421, 127-8. 7. Murata, K., Mitsuoka, K., Hirai, T., Walz, T., Agre, P., Heymann, J. B., Engel, A. & Fujiyoshi, Y. (2000). Nature 407, 599-605. 8. Agre, P., King, L. S., Yasui, M., Guggino, W. B., Ottersen, O. P., Fujiyoshi, Y., Engel, A. & Nielsen, S. (2002). J Physiol 542, 3-16. 9. Sui, H., Han, B. G., Lee, J. K., Walian, P. & Jap, B. K. (2001). Nature 414, 872-878. 10. de Groot, B. L. & Grubmuller, H. (2001). Science 294, 2353-7. 11. Chakrabarti, N., Tajkhorshid, E., Roux, B. & Pomes, R. (2004). Structure 12, 65-74.

Nanotech 2004 Conference Technical Program Abstract

 
Sponsors
Nanotech Sponsors
News Headlines
NSTI Online Community
 
 

© Nano Science and Technology Institute, all rights reserved.
Terms of use | Privacy policy | Contact