Molecular Biophysics I
2005
Sessions #11 & 12

Membrane Structure
and
Membrane Proteins: Synthesis and Insertion

Instructor: M. L. Jennings, Ph.D.

 April 13, 2005: BioMed B200    April 20, 2005: BioMed 205/207

1:00 p.m. - 3:50 p.m.

 

In the next two sessions we will discuss some general principles of membrane structure, including the structure and dynamics of lipids, membrane fluidity, lipid asymmetry, membrane protein topology and structure, and membrane protein synthesis and insertion.  In the past 5  years there have been some dramatic breakthroughs in the determination of membrane protein structure, and the emphasis of these classes has shifted to include the new structural studies. 

Selected references on these topics are listed below.  

April 13, 2005

Classic Papers on Membrane Proteins:

Singer, S.J. and Nicolson, G.L.   The fluid mosaic model of the structure of cell membranes. Science 175: 720-731, 1972.  (This is the paper that defined the concept of integral and peripheral membrane proteins.)

Bordier, C.   Phase separation of integral membrane proteins in Triton X-114 solution.  J. Biol. Chem. 256(4):  1604-1677, 1981.  (Paper describing an experimental way to distinguish integral from peripheral membrane proteins.)

Kyte, J. and Doolittle, R.F.   A simple method for displaying the hydropathic character of a protein. J.Mol.Biol. 157: 105-132, 1982.  (Original paper describing the hydropathy plot.)

 

K+ Channel Protein Structure:

Doyle, D.A., Cabral, J.M., Pfuetzner, R.A., Kuo, A., Gulbis, J.M., Cohen, S.L., Chait, B.T., and MacKinnon, R. The structure of the potassium channel:  Molecular basis of K+ conduction and selectivity.  Science 280: 69-77, 1998.  (Breakthrough paper on the structure or a potasssium channel.)

 

Structure of Calcium Pump:

MacLennan, D.H., Rice, W.J., and Green, N.M..  The mechanism of Ca2+ transport by sarco(endo)plasmic reticulum Ca2+-ATPases.   J Biol Chem. 272:28815-28818,1997.

Zhang, P., Toyoshima, C., Yonekura, K., Green, N.M., and Stokes D.L.  Structure of the calcium pump from sarcoplasmic reticulum at 8 Å resolution.  Nature 392: 835-839, 1998.

Toyoshima, C., Nakasako, M., Nomura, H., and Ogawa, H.  Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution.  Nature 405:647-655, 2000.

Toyoshima,T. and Nomura, H.  Structural changes in the calcium pump accompanying the dissociation of calcium.  Nature 418: 605-611, 2002.

F0F1 ATP Synthase as a Molecular Machine:

Elston, T., Wang, H., and Oster, G.   Energy transduction in ATP synthase. Nature 391:  510-533, 1998.  (Rotor/stator model of chemiosmotic energy transduction.)

Wang, H. and Oster, G.   Energy transduction in the F1 motor of ATP synthase.  Nature 396:  279-822, 1998.  (Elaboration on rotor/stator model of ATP synthase.)

Noji, H. and Yoshida, M.  The rotary machine in the cell, ATP synthase.  J. Biol. Chem. 276: 1665-1668, 2001.  (Review of rotary motion of the F1 ATP synthase.)


April 20, 2005

Membrane Protein Synthesis/Insertion:

von Heijne, G.   Membrane protein structure prediction: Hydrophobicity analysis and the "positive inside" rule. J.Mol.Biol. 225: 487-494, 1992.  (One of several reviews by von Heijne on the "positive inside" rule.)

Traxler, B., Boyd, D., and Beckwith, J.   The topological analysis of integral cytoplasmic membrane proteins. J.  Membrane Biol. 132: 1-11, 1993.  (Excellent description of a method for analyzing membrane protein topology based on molecular genetics.)

Wickner, W.T. and Lodish, H.F.   Multiple mechanisms of  protein insertion into and across membranes. Science 230: 400-477, 1985.  (Excellent early review of basic mechanisms of generating varied protein topology using the same machinery.)

Goder, V., Bieri, C., and Spiess, M. Glycosylation can influence topogenesis of membrane proteins and reveals dynamic reorientation of nascent polypeptides within the translocon.  J.Cell Biol., 147: 257-266, 1999.  (Recent paper on events involved in topogenesis.)

Johnson, A.E. and van Waes, M.A.  The translocon: A dynamic gateway to the ER membrane.  Annu. Rev. Cell Dev. Biol. 15: 799-842, 1999.  (Review of the translocon from a biophysical perspective.)

Higy, M., Junne, T., and Spiess, M.  Topogenesis of membrane proteins at the endoplasmic reticulum.  Biochemistry 43: 12716-12722, 2004.  (Recent review on translocon structure and function.)

White, S.H. and von Heijne, G. The machinery of membrane protein assembly.  Curr. Opinion Struct. Biol. 14: 397-404: 2004.  (Recent review of translocon structure and protein synthesis-insertion.)

MacKinnon, R.  Membrane protein insertion and stability.  Science 307: 1425-1426, 2005.  (Very recent commentary on stability of transmembrane helices.)

Glycerol and Cl- Channel Protein Structures

Heymann, J.B. and Engel, A.   Structural clues in the sequences of the aquaporins.  J. Mol. Biol. 295: 1039-1053, 2000.  (Good example of the use of bioinformatics to infer structural information.)

Fu , D., Libson, A., Miercke, L.J., Weitzman, C., Nollert, P., Krucinski, J., and Stroud, R.M. Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290: 481-486, 2000.

Dutzler, R., Campbell, E.B., Cadene, M., Chait, B.T., and MacKinnon, R.  X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity.
Nature 415:287-294, 2002.  (Recent crystal structure of a chloride channel.)

Dutzler, R., Campbell, E.B., and MacKinnon, R.  Gating the selectivity filter in ClC chloride channels.  Science 300: 108-112, 2003.  (Recent structural study of channel gating.)