Relationship between nuclear magnetic resonance chemical shift and protein secondary structure

TLDR

Prior studies on smaller datasets of 13C and 15N shifts have shown strong correlations with protein secondary structure. The study demonstrates that 1H, amide, 13C, and 15N chemical shifts exhibit strong, predictable shifts with secondary structure, with α‑helices causing an average 0.39 ppm upfield shift and β‑strands a 0.37 ppm downfield shift, and additional correlations linking shifts to helix dipole, backbone flexibility, dihedral angles, and hydrogen bonding.

Abstract

An analysis of the 1H nuclear magnetic resonance chemical shift assignments and secondary structure designations for over 70 proteins has revealed some very strong and unexpected relationships. Similar studies, performed on smaller databases, for 13C and 15N chemical shifts reveal equally strong correlations to protein secondary structure. Among the more interesting results to emerge from this work is the finding that all 20 naturally occurring amino acids experience a mean αa-1H upfield shift of 0.39 parts per million (from the random coil value) when placed in a helical configuration. In a like manner, the α-1H chemical shift is found to move downfield by an average of 0.37 parts per million when the residue is placed in a β-strand or extended configuration. Similar changes are also found for amide 1H, carbonyl 13C, α-13C and amide 15N chemical shifts. Other relationships between chemical shift and protein conformation are also uncovered; in particular, a correlation between helix dipole effects and amide proton chemical shifts as well as a relationship between α-proton chemical shifts and main-chain flexibility. Additionally, useful relationships between α-proton chemical shifts and backbone dihedral angles as well as correlations between amide proton chemical shifts and hydrogen bond effects are demonstrated.