Membrane proteins folding

J.-L. Popot, D. M. Engelman (2000) Helical membrane protein folding, stability and evolution. Annu. Rev. Biochem., 69 881-923... 

Taylor, W., Jones, D., and Green, N. (1994). A method for a-helical integral membrane protein fold prediction. Proteins Struct. Fund. Genet. 18, 281-294. 

Fig. 4. Thermodynamic models of membrane protein folding. (A) In the two-step model of folding, the TM helices fold and insert into the membrane and subsequently move laterally to associate (Popot and Engelman, 1990). (B) White and co-workers constructed an expanded model, which includes the protein residing in water (states 1-3), the interfacial region (states 4 and 5), and the membrane core (states 6 and 7) (White and Wimley, 1999).

Bowie, J. U. (1999). Helix-bundle membrane protein fold templates. Protein Sd. 8, 2711-2719. 

Popot JL. Membrane protein folding beyond the two stage model. 28. FEBS Lett 2003 555 122-125. 

North B, Cristian L, Fu Stowell X, Lear ID, Saven JG, Degrade 35. WF. Characterization of a membrane protein folding motif, the Ser zipper, using designed peptides. J. Mol. Biol. 2006 359 930-939. 

Bowie JU. Solving the membrane protein folding problem. Nature 2005 438 581-589. 

S.H. White and W.C. Wimley. 1999. Membrane protein folding and stability Physical principles Annu. Rev. Biophys. Biomol. Struct. 28 319-365. (PubMed)... 

Booth PJ, Riley ML, Flitsch SL, Templet RH, Farooq A, Curran AR, Chadborn N, Wright P (1997) Evidence that bUayer bending rigidity affects membrane protein folding. Biochemistry 36 197-203... 

Keywords Membrane protein folding phosphatidylethanolamine cardiolipin mitochondria oxidative phosphorylation... 

Lipids have multiple functions in cells ranging from defining the bilayer permeability barrier of cell membranes and organelles to providing the matrix within which membrane proteins fold and function to being integral components of... 

A specific phospholipid requirement has been determined for optimum in vitro reconstitution of function for more than 50 membrane proteins. If one considers specific lipid requirements for membrane association and activation of amphitropic proteins, the number is in hundreds. Integral membrane proteins fold and exist in a very complex environment and have three modes of interaction with their environment. The extramembrane domains are exposed to the water milieu, where they interact with water, solutes, ions, and water-soluble proteins. Part of the protein is exposed to the hydrophobic-aqueous interface region (Fig. 9). The remainder of the protein is buried within the approximately 30-A thick hydrophobic interior of the membrane. Amphitropic proteins may spend part of their time completely in the cytosol and are recruited to the membrane surface, or even partially inserted into the membrane, in response to various signals. 

Popot JL (1993) Integral membrane protein structure Transmembrane alpha-helices as autonomous folding domains. Curr Opin Struct Biol 3 532-540 Popot JL and Engelman DM (1990) Membrane protein folding and oligomerization The two-stage model. Biochemistry 29 4031-4037... 

FKBP13 13 Nonspecific ER membrane, erythrocyte membrane Protein folding and trafficking function as a component of membrane cytoskeletal scaffolds Contains ER retention signal interacts with a homologue of erythrocyte membrane cytoskeletal protein 4.1 111, 112... 

Volkov A, Dockter C, Polyhach Y, Paulsen H, Jeschke G (2010) Site-specific information on membrane protein folding by electron spin echo envelope modulation spectroscopy. J Phys Chem Lett l(3) 663-667... 

Many examples exist of highly functional complex nanoscale structures formed via self-assembly processes such as the lipid bilayer membrane, protein folding, DNA and RNA, and viruses (Boeckl and Graham, 2006 Mendes et al., 2013). Although this is a widely observed phenomenon, it is still not fuUy understood. In general, self-assembly is governed by inter- and intramolecular forces to create thermodynamically more stable structures (Boeckl and Graham, 2006). 

Khanal, A., Pan, Y., Brown, L.S., Konermann, L. (2012) Pulsed hydrogen/deuterium exchange mass spectrometry for time-resolved membrane protein folding studies. Journal of Mass Spectrometry, 47 (12), 1620-1626. 

Electron Spin Echo Envelope Modulation, or ESEEM, is widely used to investigate structure of the immediate surroundings of paramagnetic species. In combination with site-specific spin labeling and selective deuterium substitution, it becomes a helpful tool to study location of proteins and small peptides within membranes, interaction of small molecules with proteins, supramolecular assemblies, water accessibility to specific regions of proteins and water penetration into membranes, protein folding and secondary structures. In this review, experimental approaches and limitations, theoretical background of the method, and recent applications are discussed. 

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