October 2009 news and views

Research highlights

PSI-SGKB [doi:10.1038/nchembio0909-614-psi]

Core considerations

Michael Giuliano

Protein stability depends on a variety of intermolecular forces, including van der Waals packing interactions in the protein core. While the strength of these interactions is well documented for soluble, natural proteins, it is not as clear how van der Waals forces extend to membrane proteins and to non-natural systems. Joh et al. now determine the crystal structures of six bacteriorhodopsin mutants, each of which introduces a smaller amino acid to create a hole in the protein structure. A comparison of the cavity sizes created by the mutations with the overall stability of the protein yielded correlations that were within error of those observed previously for the soluble T4 lysozyme, which suggests that natural protein packing is independent of environmental context. In contrast, Giuliano et al. discovered that replacing the residues at the a and d positions of an engineered tetrameric parallel helical bundle with β-amino acids caused a significant change in packing. In this case, the helices form an antiparallel structure in which helix dimers are in very close contact. These dimers create a flat hydrophobic surface that pairs with a second dimer like a sandwich, rather than the 'knobs and holes' packing typical of α-amino acid bundles. These studies should provide new insights into protein structure and design. (J. Am. Chem. Soc., 131, 9860–9861, 2009; J. Am. Chem. Soc., published online 15 July 2009, doi:10.1021/ja904711k) CG