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PDBsum entry 5mfc
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De novo protein
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PDB id
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5mfc
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References listed in PDB file
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Key reference
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Title
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Structures of designed armadillo repeat proteins binding to peptides fused to globular domains.
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Authors
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S.Hansen,
J.D.Kiefer,
C.Madhurantakam,
P.R.E.Mittl,
A.Plückthun.
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Ref.
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Protein Sci, 2017,
26,
1942-1952.
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PubMed id
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Abstract
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Designed armadillo repeat proteins (dArmRP) are α-helical solenoid repeat
proteins with an extended peptide binding groove that were engineered to develop
a generic modular technology for peptide recognition. In this context, the term
"peptide" not only denotes a short unstructured chain of amino acids,
but also an unstructured region of a protein, as they occur in termini, loops,
or linkers between folded domains. Here we report two crystal structures of
dArmRPs, in complex with peptides fused either to the N-terminus of Green
Fluorescent Protein or to the C-terminus of a phage lambda protein D. These
structures demonstrate that dArmRPs bind unfolded peptides in the intended
conformation also when they constitute unstructured parts of folded proteins,
which greatly expands possible applications of the dArmRP technology.
Nonetheless, the structures do not fully reflect the binding behavior in
solution, that is, some binding sites remain unoccupied in the crystal and even
unexpected peptide residues appear to be bound. We show how these differences
can be explained by restrictions of the crystal lattice or the composition of
the crystallization solution. This illustrates that crystal structures have to
be interpreted with caution when protein-peptide interactions are characterized,
and should always be correlated with measurements in solution.
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