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Science 2 December 2005:
Vol. 310. no. 5753, pp. 1452 - 1456
DOI: 10.1126/science.1113752
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Review

Protein Translocation Across Biological Membranes

William Wickner1* and Randy Schekman2*

Subcellular compartments have unique protein compositions, yet protein synthesis only occurs in the cytosol and in mitochondria and chloroplasts. How do proteins get where they need to go? The first steps are targeting to an organelle and efficient translocation across its limiting membrane. Given that most transport systems are exquisitely substrate specific, how are diverse protein sequences recognized for translocation? Are they translocated as linear polypeptide chains or after folding? During translocation, how are diverse amino acyl side chains accommodated? What are the proteins and the lipid environment that catalyze transport and couple it to energy? How is translocation coordinated with protein synthesis and folding, and how are partially translocated transmembrane proteins released into the lipid bilayer? We review here the marked progress of the past 35 years and salient questions for future work. Subcellular compartments have unique protein compositions, yet protein synthesis only occurs in the cytosol and in mitochondria and chloroplasts. How do proteins get where they need to go? The first steps are targeting to an organelle and efficient translocation across its limiting membrane. Given that most transport systems are exquisitely substrate specific, how are diverse protein sequences recognized for translocation? Are they translocated as linear polypeptide chains or after folding? During translocation, how are diverse amino acyl side chains accommodated? What are the proteins and the lipid environment that catalyze transport and couple it to energy? How is translocation coordinated with protein synthesis and folding, and how are partially translocated transmembrane proteins released into the lipid bilayer? We review here the marked progress of the past 35 years and salient questions for future work.

1 Department of Biological Chemistry, Dartmouth Medical School, 7200 Vail Building, Hanover, NH 03755–3844, USA.
2 Howard Hughes Medical Institute and Department of Molecular and Cell Biology, 626 Barker Hall, University of California, Berkeley, CA 94720–3202, USA.

Note added in proof: For more on SecYEG structure, see K. Mitra et al., Nature 438, 318 (2005).

* To whom correspondence should be addressed. E-mail: Bill.Wickner{at}Dartmouth.edu (W.W.); schekman{at}berkeley.edu (R.S.)

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