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Solving the membrane protein folding problem

Abstract

One of the great challenges for molecular biologists is to learn how a protein sequence defines its three-dimensional structure. For many years, the problem was even more difficult for membrane proteins because so little was known about what they looked like. The situation has improved markedly in recent years, and we now know over 90 unique structures. Our enhanced view of the structure universe, combined with an increasingly quantitative understanding of fold determination, engenders optimism that a solution to the folding problem for membrane proteins can be achieved.

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Figure 1: Progress of helix bundle membrane protein structure determination.
Figure 2: The structure of the glycerol channel GlpF.
Figure 3: Two stages of membrane protein folding10.
Figure 4: A snapshot of a molecular dynamics simulation of a POPC bilayer16.
Figure 5: Free energies for transfer of amino acids from water to octanol15.
Figure 6: The Sec61 translocon structure and mechanism model23.
Figure 7: The glycophorin A dimer89.
Figure 8: Curvature elastic energy.
Figure 9: Hydrophobic mismatch.

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Acknowledgements

I would like to thank members of my lab for helpful comments and NIH for support. J.U.B. is a Leukemia and Lymphoma Society Scholar.

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Bowie, J. Solving the membrane protein folding problem. Nature 438, 581–589 (2005). https://doi.org/10.1038/nature04395

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