Organisers

• Jeremy Smith (University of Heidelberg)
• Gunnar von Heijne (Stockholm University)
• Stephen H White (University of California at Irvine)
• Ana-Nicoleta Bondar (University of California at Irvine)

Supports

 CECAM

Description

Membrane protein assembly is an extremely complex cellular process during which the translocon machinery incorporates newly synthesized membrane proteins into the lipid bilayer. Key open issues include i) what is the oligomeric state of the functioning translocon; ii) how the interaction between the membrane-embedded translocon and the signal peptide triggers a conformational change ultimately leading to the opening of the translocon; iii) what is the conformation of the open-state translocon; iv) are the hydrophobic newly synthesized peptides exposed to an aqueous milieu inside the translocon, and how do they partition into the lipid membrane; v) what determines the insertion into the lipid membrane of helices containing polar residues, and vi) how the lipid bilayer participates to membrane protein assembly.

Computer simulations are critical to understand the energetics and the pathway of newly synthesized proteins through the translocon to their final destination in the lipid membrane. Exciting recent developments from the experimental studies (e.g., crystal structures of wild-type and mutant translocon phenotypes, identification of the translocon:signal peptide contacts) challenge some of the views held on the mechanism of membrane protein assembly.

Scientific Objectives

The ambitious aim of the workshop is to provide a unique opportunity for outstanding theoreticians and experimentalists to discuss the state of the art in the field of membrane protein assembly. We invited experts active in the theoretical and experimental fields, but we plan to also encourage junior researchers to participate and present their results. The open discussions throughout the meeting should catalyze collaborative research and lead to new ideas of computations and experiments in this fundamental area of research.

The workshop will focus on the following aspects:
- Architecture and dynamics of the protein translocation machinery
- Challenges in computational studies of membrane-embedded protein complexes
- Energetics of membrane protein insertion, lipid-protein interactions, peptides at interfaces
- Challenges in computational studies of protein conformational changes. Conformational changes of peptides inside the membrane protein insertion apparatus
- Dynamics of protein-protein interactions and role of protein-protein interactions in membrane protein assembly.

References

1. Membrane protein insertion: the biology-physics nexus. S. H. White, J. Gen. Physiol. 129:363-369 (2007).
2. Recognition of transmembrane helices by the endoplasmic reticulum translocon. T. Hessa, H. Kim, K. Bihlmaier, C. Lundin, J. Boekel, H. Andersson, I. Nilsson, S. H. White, and G. von Heijne, Nature 433: 377-381.
3. Interface connections of a transmembrane voltage sensor. J. A. Freites, D. J. Tobias, G. von Heijne, and S. H. White. Proc. Natl. Acad. Sci. USA 102: 15059-15064 (2005).
4. The plug domain of the SecY protein stabilizes the closed state of the translocation channel and maintains a membrane seal. L. Weikai, S. Schulman, D. Boyd, K. Erlandson, J. Beckwith, and T. A. Rapoport. Mol. Cell 26: 511-521 (2007).
5. Structural determinants of the lateral gate opening in the protein translocon. J. Gumbart and K. Schulten, Biochemistry 46, 11147-11157 (2007).
6. Simulations of a protein translocation pore: SecY. S. Haider, B. A. Hall, and M. S. P. Sansom, Biochemistry 45, 13018-13024 (2006).
7. On the thermodynamic stability of a charged arginine side chain in a transmembrane helix. S. Dorairaj and T. W. Allen. Proc. Natl. Acad. Sci. USA 104, 4943-4948 (2007).
8. Partitioning of amino acid sidechains into lipid bilayers: results from computer simulations and comparison to experiment. J. L. MacCallum, W. F. D. Bennett, and D. P. Tieleman, J. Gen. Physiol. 129, 371-377 (2007).