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PDBsum entry 2x7z
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Structural protein
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PDB id
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2x7z
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References listed in PDB file
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Key reference
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Title
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The plastic energy landscape of protein folding: a triangular folding mechanism with an equilibrium intermediate for a small protein domain.
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Authors
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S.R.Haq,
M.C.Jürgens,
C.N.Chi,
C.S.Koh,
L.Elfström,
M.Selmer,
S.Gianni,
P.Jemth.
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Ref.
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J Biol Chem, 2010,
285,
18051-18059.
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PubMed id
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Abstract
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Protein domains usually fold without or with only transiently populated
intermediates, possibly to avoid misfolding, which could result in amyloidogenic
disease. Whether observed intermediates are productive and obligatory species on
the folding reaction pathway or dispensable by-products is a matter of debate.
Here, we solved the crystal structure of a small protein domain, SAP97 PDZ2
I342W C378A, and determined its folding pathway. The presence of a folding
intermediate was demonstrated both by single and double-mixing kinetic
experiments using urea-induced (un)folding as well as ligand-induced folding.
This protein domain was found to fold via a triangular scheme, where the folding
intermediate could be either on- or off-pathway, depending on the experimental
conditions. Furthermore, we found that the intermediate was present at
equilibrium, which is rarely seen in folding reactions of small protein domains.
The folding mechanism observed here illustrates the roughness and plasticity of
the protein folding energy landscape, where several routes may be employed to
reach the native state. The results also reconcile the folding mechanisms of
topological variants within the PDZ domain family.
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