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  • Title: C-capping and helix stability: the Pro C-capping motif.
    Author: Prieto J, Serrano L.
    Journal: J Mol Biol; 1997 Nov 28; 274(2):276-88. PubMed ID: 9398533.
    Abstract:
    Here we have performed a statistical analysis of the protein database to find new putative local C-terminal motifs in alpha-helices. Our analysis shows that certain combinations of X-Pro pairs (Asn, Cys, His, Phe, Tyr, Trp, Ile, Val and Leu), in which residue X is the C-cap and the Pro is at position C', are more abundant than expected. In those pairs, except for the aliphatic residues, the presence of the Pro residue at C' tends to restrict the phi and psi dihedral angles of the residue at position C-cap, around -130 degrees , 70 degrees , respectively. For the aromatic residues as well as for His, the chi1 angle is around -60 degrees and the edge of the His and aromatic rings are close to the carbonyl group of the residue i - 4. In all the pairs having the above dihedral angles for residue C-cap, the main-chain amino group of Pro at C' is close to the last three main-chain carbonyls of the alpha-helix. The above structural arrangements suggests the existence of a stabilising electrostatic interaction of the residues at positions C-cap and C' with the helix macrodipole. We have denominated this putative local motif, the Pro-capping motif. To asses its importance in helix stability we have analysed by nuclear magnetic resonance (NMR) and far-UV circular dichroism (CD) a set of polyalanine-based peptides containing two of the above pairs: His-Pro and Phe-Pro, as well as the corresponding controls. In the case of the His-Pro pair we have found NMR evidence for the formation of the Pro-capping motif in aqueous solution. CD analysis shows that the presence of a Pro residue alters the C-cap properties of the preceding amino acids in the case of His and Phe makes them more favourable. The Pro-capping motif with the appropriate sequence, determines the location of the C terminus of alpha-helices and stabilises the helical conformation having Pro as the C' residue.
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