TY - JOUR
T1 - Sequence and Structure Analysis of Parallel β Helices
T2 - Implication for Constructing Amyloid Structural Models
AU - Tsai, Hui Hsu (Gavin)
AU - Gunasekaran, Kannan
AU - Nussinov, Ruth
N1 - Funding Information:
We thank Dr. C.-J Tsai for discussion. H.-H.T. gratefully acknowledges the support from the National Science Council (grant no.: NSC 94-2119-M-008-020) and National Central University, Taiwan. The research of R.N. in Israel has been supported in part by the “Center of Excellence in Geometric Computing and its Applications” funded by the Israel Science Foundation (administered by the Israel Academy of Sciences), and by the Adams Brain Center. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health (NIH), under contract number NO1-CO-12400. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organization imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
PY - 2006/6
Y1 - 2006/6
N2 - Increasing evidence suggests that amyloids and parallel β helices may share similar motifs. A systemic analysis of β helices is performed to examine their sequence and structural characteristics. Ile prefers to occur in β strands. In contrast, Pro is disfavored, compatible with the underlying assumption in Pro-scanning mutagenesis. Cys, Asn, and Phe form significant homostacking (identical amino acid interactions). Asn is highly conserved in the high-energy, left-handed α-helical conformation, where it frequently forms amide stacking. Based on the observed prominent stacking of chemically similar residues in parallel β helices, we propose that within the "cross-β" framework, amyloids with longer peptide chains may have common structural features of in-register, parallel alignment, with the side chains forming identical amino acid ladders. The requirement of ladder formation limits the combinations of side chain interactions. Such a limit combined with environmental conditions (e.g., pH, concentration) could be a major reason for the ability of most polypeptides to form amyloids.
AB - Increasing evidence suggests that amyloids and parallel β helices may share similar motifs. A systemic analysis of β helices is performed to examine their sequence and structural characteristics. Ile prefers to occur in β strands. In contrast, Pro is disfavored, compatible with the underlying assumption in Pro-scanning mutagenesis. Cys, Asn, and Phe form significant homostacking (identical amino acid interactions). Asn is highly conserved in the high-energy, left-handed α-helical conformation, where it frequently forms amide stacking. Based on the observed prominent stacking of chemically similar residues in parallel β helices, we propose that within the "cross-β" framework, amyloids with longer peptide chains may have common structural features of in-register, parallel alignment, with the side chains forming identical amino acid ladders. The requirement of ladder formation limits the combinations of side chain interactions. Such a limit combined with environmental conditions (e.g., pH, concentration) could be a major reason for the ability of most polypeptides to form amyloids.
UR - http://www.scopus.com/inward/record.url?scp=33744807442&partnerID=8YFLogxK
U2 - 10.1016/j.str.2006.03.015
DO - 10.1016/j.str.2006.03.015
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AN - SCOPUS:33744807442
SN - 0969-2126
VL - 14
SP - 1059
EP - 1072
JO - Structure
JF - Structure
IS - 6
ER -