Translocon language


Reprinted by permission of Macmillian Publishers, LTD.

The paper:

T. Hessa et al., ?Recognition of transmembrane helices by the endoplasmic reticulum translocon,? Nature, 433:377?81, 2005. (Cited in 88 papers) | [PubMed]

The finding:

Gunnar von Heijne at Stockholm University and colleagues systematically altered the sequence of a transmembrane helix segment to understand how the translocon protein complex determines the segment?s placement in a lipid membrane. ?We figured out how to speak to the translocon, and we?re learning what its code is for inserting transmembrane proteins,? says co-author Stephen White from the University of California, Irvine.

The surprise:

It was easy to imagine that a peptide?s interaction with the translocon determined a segment?s location, says von Heijne. But this paper provided evidence that the protein?s interactions with the lipid bilayer are directing the translocon.

The follow-up:

Von Heijne has tested several hundred additional polypeptides in various systems, such as Escherichia coli, to see if the translocon?s thermodynamic decision-making is consistent. All the data, he says, support the 2005 findings. Petra Fromme at Arizona State University says these ?general principles of transmembrane protein insertion? have allowed her to predict transmembrane proteins in blue-green algae.

The challenge:

The authors? system used a single helix, whereas in vivo, helix-helix interactions might alter the way the translocon handles the peptides. ?Transmembrane helices don?t always insert into the membrane when you take them out of context,? von Heijne says. Trying to model multi-helix interactions ?brings in a whole new level of complexity.?

The numbers:
Free energy range Peptides Favored position
<0 kcal/mol Isoleucine-Valine Hydrocarbon core
-0 kcal/mol Cysteine-Alanine Interfacial region
>0 kcal/mol Charged and polar residues Aqueous layer



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