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PDBsum entry 2oop
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References listed in PDB file
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Key reference
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Title
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Probing the formation of stable tertiary structure in a model miniprotein at atomic resolution: determinants of stability of a helical hairpin.
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Authors
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A.Neumoin,
J.Mares,
M.Lerch-Bader,
R.Bader,
O.Zerbe.
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Ref.
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J Am Chem Soc, 2007,
129,
8811-8817.
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PubMed id
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Abstract
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The minimal model system to study the basic principles of protein folding is the
hairpin. The formation of beta-hairpins, which are the basic components of
antiparallel beta-sheets, has been studied extensively in the past decade, but
much less is known about helical hairpins. Here, we probe hairpin formation
between a polyproline type-II helix and an alpha-helix as present in the natural
miniprotein peptide YY (PYY). Both turn sequence and interactions of aromatic
side chains from the C-terminal alpha-helix with the pockets formed by
N-terminal Pro residues are shown by site-directed mutagenesis and solution NMR
spectroscopy in different solvent systems to be important determinants of
backbone dynamics and hairpin stability, suggesting a close analogy with some
beta-hairpin structures. It is shown that multiple relatively weak contacts
between the helices are necessary for the formation of the helical hairpin
studied here, whereas the type-I beta-turn acts like a hinge, which through
certain single amino acid substitutions is destabilized such that hairpin
formation is completely abolished. Denaturation and renaturation of tertiary
structure by temperature or cosolvents were probed by measuring changes of
chemical shifts. Folding of PYY is both reversible and cooperative as inferred
from the sigmoidal denaturation curves displayed by residues at the interface of
the helical hairpin. Such miniproteins thus feature an important hallmark of
globular proteins and should provide a convenient system to study basic aspects
of helical hairpin folding that are complementary to those derived from studies
of beta-hairpins.
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