Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations. / Pedersen, Søren W; Pedersen, Stine B; Anker, Louise; Hultqvist, Greta; Kristensen, Anders S; Jemth, Per; Strømgaard, Kristian.

In: Nature Communications, Vol. 5, 3215, 2014, p. 1-11.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Pedersen, SW, Pedersen, SB, Anker, L, Hultqvist, G, Kristensen, AS, Jemth, P & Strømgaard, K 2014, 'Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations', Nature Communications, vol. 5, 3215, pp. 1-11. https://doi.org/10.1038/ncomms4215

APA

Pedersen, S. W., Pedersen, S. B., Anker, L., Hultqvist, G., Kristensen, A. S., Jemth, P., & Strømgaard, K. (2014). Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations. Nature Communications, 5, 1-11. [3215]. https://doi.org/10.1038/ncomms4215

Vancouver

Pedersen SW, Pedersen SB, Anker L, Hultqvist G, Kristensen AS, Jemth P et al. Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations. Nature Communications. 2014;5:1-11. 3215. https://doi.org/10.1038/ncomms4215

Author

Pedersen, Søren W ; Pedersen, Stine B ; Anker, Louise ; Hultqvist, Greta ; Kristensen, Anders S ; Jemth, Per ; Strømgaard, Kristian. / Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations. In: Nature Communications. 2014 ; Vol. 5. pp. 1-11.

Bibtex

@article{ae7f9ba972f14d9b9654900bd3ea47d8,
title = "Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations",
abstract = "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.",
author = "Pedersen, {S{\o}ren W} and Pedersen, {Stine B} and Louise Anker and Greta Hultqvist and Kristensen, {Anders S} and Per Jemth and Kristian Str{\o}mgaard",
year = "2014",
doi = "10.1038/ncomms4215",
language = "English",
volume = "5",
pages = "1--11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations

AU - Pedersen, Søren W

AU - Pedersen, Stine B

AU - Anker, Louise

AU - Hultqvist, Greta

AU - Kristensen, Anders S

AU - Jemth, Per

AU - Strømgaard, Kristian

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms4215

DO - 10.1038/ncomms4215

M3 - Journal article

C2 - 24477114

VL - 5

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3215

ER -

ID: 108650774