Structural highlights
Publication Abstract from PubMedMiniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPalpha-Tyr, a designed peptide comprising an alpha-helix buttressed by a polyproline II helix. PPalpha-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 degrees C. NMR structures of PPalpha-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPalpha is sensitive to modifications in the aromatic residues: replacing tyrosine with phenylalanine, i.e., changing three solvent-exposed hydroxyl groups to protons, reduces the TM to 20 degrees C. We attribute this result to the loss of CH-pi interactions between the aromatic and proline rings, which we probe by substituting the aromatic residues with nonproteinogenic side chains. In analyses of natural protein structures, we find a preference for proline-tyrosine interactions over other proline-containing pairs, and observe abundant CH-pi interactions in biologically important complexes between proline-rich ligands and SH3 and similar domains. Engineering protein stability with atomic precision in a monomeric miniprotein.,Baker EG, Williams C, Hudson KL, Bartlett GJ, Heal JW, Porter Goff KL, Sessions RB, Crump MP, Woolfson DN Nat Chem Biol. 2017 Jul;13(7):764-770. doi: 10.1038/nchembio.2380. Epub 2017 May , 22. PMID:28530710[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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