Type VIa β‐turn‐fused helix N‐termini: A novel helix N‐cap motif containing cis proline. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Dasgupta, Rubin; Ganguly, Himal K.; Modugula, E. K.; Basu, Gautam
• Other Names: Toniolo Claudio guestEditor.; Ganesh Krishna guestEditor.; Gopi Hosahudya guestEditor.; Balaram P. guestEditor.
• Is Part Of: Biopolymers. Volume 108:Issue 1(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-01
• Subjects: helix N‐cap -- cis Proline -- sequence motif; Biopolymers -- Periodicals; Peptides -- Periodicals; Spectrum analysis -- Periodicals; 572.33
• DOI: 10.1002/bip.22919
• Languages: English
• ISSNs: 0006-3525

Abstract

Abstract: 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 (αR or PPII ) often appears at the N‐cap position (N0) of helices. The N‐cap cis Pro(αR ) 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(αR ) 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(αR ) 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.