TY - JOUR
T1 - Spectral analysis of a protein conformational switch
AU - Rackovsky, S.
PY - 2011/6/14
Y1 - 2011/6/14
N2 - The existence of conformational switching in proteins, induced by single amino acid mutations, presents an important challenge to our understanding of the physics of protein folding. Sequence-local methods, commonly used to detect structural homology, are incapable of accounting for this phenomenon. We examine a set of proteins, derived from the GA and GB domains of Streptococcus protein G, which are known to show a dramatic conformational change as a result of single-residue replacement. It is shown that these sequences, which are almost identical locally, can have very different global patterns of physical properties. These differences are consistent with the observed complete change in conformation. These results suggest that sequence-local methods for identifying structural homology can be misleading. They point to the importance of global sequence analysis in understanding sequence-structure relationships.
AB - The existence of conformational switching in proteins, induced by single amino acid mutations, presents an important challenge to our understanding of the physics of protein folding. Sequence-local methods, commonly used to detect structural homology, are incapable of accounting for this phenomenon. We examine a set of proteins, derived from the GA and GB domains of Streptococcus protein G, which are known to show a dramatic conformational change as a result of single-residue replacement. It is shown that these sequences, which are almost identical locally, can have very different global patterns of physical properties. These differences are consistent with the observed complete change in conformation. These results suggest that sequence-local methods for identifying structural homology can be misleading. They point to the importance of global sequence analysis in understanding sequence-structure relationships.
UR - http://www.scopus.com/inward/record.url?scp=79960634758&partnerID=8YFLogxK
U2 - 10.1103/PhysRevLett.106.248101
DO - 10.1103/PhysRevLett.106.248101
M3 - Article
AN - SCOPUS:79960634758
SN - 0031-9007
VL - 106
JO - Physical Review Letters
JF - Physical Review Letters
IS - 24
M1 - 248101
ER -