Thesis subject
Modeling membrane protein structure through site-directed ESR spectroscopy
PhD Thesis Aleh Kavalenka, September 30, 2009
Proteins are the key molecules in cells of living organisms, including human beings. They participate for instance in signaling pathways, intracellular and extracellular transport, mechanical work, and can act as sensors. Biochemistry, and particularly the knowledge about protein structure and function, provides important insights and practical applications in medicine, agriculture, nutrition, and industry 1. Our special interest in this thesis concerns the study of structural characteristics of membrane proteins and intrinsically disordered proteins, which have been characterized far less well than water-soluble proteins.
We describe a new modeling approach for membrane protein structure characterization based on a) structural constraints experimentally determined by sitedirected labeling; b) conformational space modeling; c) protein structure optimization. The first chapter is a general introduction to the structural organization of proteins, in particular membrane proteins, and to the techniques, which have been used to study these protein systems. Later on in the thesis the focus will be on site-directed spin labeling (SDSL) electron spin resonance (ESR) spectroscopy, an alternative and complementary technique with respect to well-established and powerful techniques like X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy.
First, in section 1.1 some background information is presented about proteins and biological membranes. Section 1.2 describes different experimental techniques used for protein structure determination. In section 1.3 the protein structure modeling is overviewed.
The next two sections describe the two membrane proteins: bacteriophage M13 coat protein (section 1.4), and light-harvesting protein complex CP29 (section 1.5), which are studied in detail in this thesis. Finally, section 1.6 introduces the overview of the thesis.