Biological Physics: Folding of membrane proteins

 

Proteins, RNAs and DNAs are biological polymers. Membrane consisting of lipid bilayer is a cell wall with complicated architecture, which divides the cell interior from the extracellular environment. All together, proteins, lipids of membrane, RNA and DNA make up cells, organs and organisms. Biological function is determined by the interaction between proteins, proteins and membrane, proteins and RNA and DNA. Proteins have ability to form unique 3-D structure, the process termed folding. Unique 3-D structure determines the specific functions of proteins. All proteins could be divided into two big groups depending on the environment where they exist: water-soluble (inside and outside of cell) and membrane proteins (anchored to cell membrane). The membrane proteins are responsible for the transduction of all signals from outside to inside a cell and vice versa. One of he major goals of our research is to understand general principles of folding and organization of membrane proteins. We study membrane peptide, pHLIP (pH Low Insertion Peptide), which posses unique properties that are extremely useful for the biophysical studies of the folding of membrane proteins in vitro: pHLIP is soluble in aqueous solution, and has ability to insert spontaneously, fast (seconds), and reversibly into lipid bilayers in a form of transmembrane helix only at low pH. At normal pH pHLIP weakly interacts with membrane surface and does not exhibit any elements of secondary structure. There are several questions, which we would like to address in our research: How does pHLIP insert into lipid bilayers and fold (forms transmembrane helix)? What is the energy of peptide attachment and insertion? How the sequence variation might affect thermodynamics and kinetics of insertion? What is triggering the process of insertion? How the peptide might disturb the lipid bilayer at low and normal pH?

 

Representative Publications:

Y.K. Reshetnyak, M. Segala, O. A. Andreev, D. M. Engelman (2007) A monomeric membrane peptide that lives in three worlds: in solution, attached to and inserted across lipid bilayers. Biophysical Journal, in press.