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Type VIa β‐turn‐fused helix N‐termini: A novel helix N‐cap motif containing cis proline
Author(s) -
Dasgupta Rubin,
Ganguly Himal K.,
Modugula E. K.,
Basu Gautam
Publication year - 2017
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22919
Subject(s) - chemistry , stereochemistry , hydrogen bond , amide , helix (gastropod) , polyproline helix , crystallography , stacking , side chain , residue (chemistry) , proline , peptide , amino acid , molecule , biochemistry , ecology , organic chemistry , snail , biology , polymer
Helix N‐capping motifs often form hydrogen bonds with terminal amide groups which otherwise would be free. Also, without an amide hydrogen, proline ( trans ) is over‐represented at helix N‐termini (N1 position) because this naturally removes the need to hydrogen bond one terminal amide. However, the preference of cis Pro, vis‐à‐vis helix N‐termini, is not known. We show that cis Pro (α R or PP II ) often appears at the N‐cap position (N0) of helices. The N‐cap cis Pro(α R ) is associated with a six‐residue sequence motif — X (‐2) –X (‐1) – cis Pro–X (1) –X (2) –X (3) — with preference for Glu/Gln at X (‐1) , Phe/Tyr/Trp at X (1) and Ser/Thr at X (3) . The motif, formed by the fusion of a helix and a type VIa β‐turn, contains a hydrogen bond between the side chain of X (‐1) and the side chain/backbone of X (3) , a α‐helical hydrogen bond between X (‐2) and X (2) and stacking interaction between cis Pro and an aromatic residue at X (1) . NMR experiments on peptides containing the motif and its variants showed that local interactions associated with the motif, as found in folded proteins, were not enough to significantly tilt the cis/trans equilibrium towards cis Pro. This suggests that some other evolutionary pressure must select the cis Pro motif (over trans Pro) at helix N‐termini. Database analysis showed that >C = O of the pre‐ cis Pro(α R ) residue at the helix N‐cap, directed opposite to the N→C helical axis, participates in long‐range interactions. We hypothesize that the cis Pro(α R ) motif is preferred at helix N‐termini because it allows the helix to participate in long‐range interactions that may be structurally and functionally important.