TY - JOUR
T1 - An amino-domino model described by a cross-peptide-bond Ramachandran plot defines amino acid pairs as local structural units
AU - Rosenberg, Aviv A.
AU - Yehishalom, Nitsan
AU - Marx, Ailie
AU - Bronstein, Alex M.
N1 - Publisher Copyright: Copyright © 2023 the Author(s).
PY - 2023
Y1 - 2023
N2 - Protein structure, both at the global and local level, dictates function. Proteins fold from chains of amino acids, forming secondary structures, α-helices and β-strands, that, at least for globular proteins, subsequently fold into a three-dimensional structure. Here, we show that a Ramachandran-type plot focusing on the two dihedral angles separated by the peptide bond, and entirely contained within an amino acid pair, defines a local structural unit. We further demonstrate the usefulness of this cross-peptide-bond Ramachandran plot by showing that it captures β-turn conformations in coil regions, that traditional Ramachandran plot outliers fall into occupied regions of our plot, and that thermophilic proteins prefer specific amino acid pair conformations. Further, we demonstrate experimentally that the effect of a point mutation on backbone conformation and protein stability depends on the amino acid pair context, i.e., the identity of the adjacent amino acid, in a manner predictable by our method.
AB - Protein structure, both at the global and local level, dictates function. Proteins fold from chains of amino acids, forming secondary structures, α-helices and β-strands, that, at least for globular proteins, subsequently fold into a three-dimensional structure. Here, we show that a Ramachandran-type plot focusing on the two dihedral angles separated by the peptide bond, and entirely contained within an amino acid pair, defines a local structural unit. We further demonstrate the usefulness of this cross-peptide-bond Ramachandran plot by showing that it captures β-turn conformations in coil regions, that traditional Ramachandran plot outliers fall into occupied regions of our plot, and that thermophilic proteins prefer specific amino acid pair conformations. Further, we demonstrate experimentally that the effect of a point mutation on backbone conformation and protein stability depends on the amino acid pair context, i.e., the identity of the adjacent amino acid, in a manner predictable by our method.
KW - Ramachandran outlier
KW - Ramachandran plot
KW - dihedral angle
KW - protein structure
KW - secondary structure
UR - http://www.scopus.com/inward/record.url?scp=85175221697&partnerID=8YFLogxK
U2 - https://doi.org/10.1073/pnas.2301064120
DO - https://doi.org/10.1073/pnas.2301064120
M3 - مقالة
C2 - 37878722
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 44
M1 - e2301064120
ER -