Abstract:
:Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 °C. NMR structures of PPα-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPα 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 °C. We attribute this result to the loss of CH-π 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-π interactions in biologically important complexes between proline-rich ligands and SH3 and similar domains.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Baker EG,Williams C,Hudson KL,Bartlett GJ,Heal JW,Porter Goff KL,Sessions RB,Crump MP,Woolfson DNdoi
10.1038/nchembio.2380subject
Has Abstractpub_date
2017-07-01 00:00:00pages
764-770issue
7eissn
1552-4450issn
1552-4469pii
nchembio.2380journal_volume
13pub_type
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