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Probing backbone hy...
Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations
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Pedersen, Soren W. (author)
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Pedersen, Stine B. (author)
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Anker, Louise (author)
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- Hultqvist, Greta (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Kristensen, Anders S. (author)
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- Jemth, Per (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Stromgaard, Kristian (author)
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(creator_code:org_t)
- 2014-01-29
- 2014
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3215-
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Abstract
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- PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions.
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- art (subject category)
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