Cell Biology

Made to Break

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Science  18 Jul 2003:
Vol. 301, Issue 5631, pp. 281
DOI: 10.1126/science.301.5631.281a

Recent determinations of protein structures have shown that transmembrane helices, previously thought to extend straight across the bilayer, can instead be bent, twisted, or even broken. These results come from proteins with multiple helices and thus may not apply to those spanning the membrane only once. Urban and Freeman highlight the dangers of intramembrane helix-breaking residues by mapping the specificity of the Drosophilarhomboid protease, one of a class of enzymes that releases membrane-bound ligands by cutting once within their single-span membrane tethers. Amino acids with small side chains (glycine and alanine) are known to destabilize helices and, when coupled to nearby nonhydrophobic residues at the extracellular surface, promote susceptibility to rhomboid. The authors also find that similar sequence motifs serve as the signals for cleavage of adhesion proteins that the intracellular parasite Toxoplasma uses to invade host cells. These findings add to the range of processes involving intramembrane proteolysis, in particular, the earlier observations by Herlan et al. and McQuibban et al. that a yeast rhomboid protease cuts a dynamin-like protein involved in regulating mitochondrial morphology. — GJC

Mol. Cell 11, 1425 (2003); J. Biol. Chem. 10.1074/jbc.M211311200 (2003); Nature 423, 537 (2003).

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