BIOCHEMISTRY: An Evolutionary Bent

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Science  30 Jan 2004:
Vol. 303, Issue 5658, pp. 591a
DOI: 10.1126/science.303.5658.591a

One of the facts that students of introductory biochemistry are taught is that proline is special because it contains a secondary amine, unlike the primary amine found in other amino acids. This difference in chemistry explains why helices that contain internal proline residues are not straight, but bent.

Using experimentally solved crystal structures of transmembrane helices as exemplars, Yohannan et al. have aligned the amino acid sequences of homologous proteins and looked at prolines. Their startling finding is that there is a strong correlation between the frequency of prolines at a position and a bend in the helix at that site, even if the helix of known three-dimensional structure does not itself contain a proline. They suggest that kinked helices lacking proline have arisen via compensatory mutations; these serve to stabilize the bent conformation (which provided an evolutionarily advantageous function) to such an extent that proline is no longer necessary. Finally, they have extended this classification to the large and pharmaceutically relevant family of G protein-coupled receptors, defining three structural groups that differ in which of the seven transmembrane helices are bent and where. — GJC

Proc. Natl. Acad. Sci. U.S.A. 101, 959 (2004).

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