Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97

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Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97. / Chi, Celestine Ngang; Bach, Anders; Engström, Åke; Strømgaard, Kristian; Lundström, Patrik; Ferguson, Neil; Jemth, Per.

In: Journal of Biological Chemistry, Vol. 286, No. 5, 04.02.2011, p. 3597-3606.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Chi, CN, Bach, A, Engström, Å, Strømgaard, K, Lundström, P, Ferguson, N & Jemth, P 2011, 'Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97', Journal of Biological Chemistry, vol. 286, no. 5, pp. 3597-3606. https://doi.org/10.1074/jbc.M110.190264

APA

Chi, C. N., Bach, A., Engström, Å., Strømgaard, K., Lundström, P., Ferguson, N., & Jemth, P. (2011). Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97. Journal of Biological Chemistry, 286(5), 3597-3606. https://doi.org/10.1074/jbc.M110.190264

Vancouver

Chi CN, Bach A, Engström Å, Strømgaard K, Lundström P, Ferguson N et al. Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97. Journal of Biological Chemistry. 2011 Feb 4;286(5):3597-3606. https://doi.org/10.1074/jbc.M110.190264

Author

Chi, Celestine Ngang ; Bach, Anders ; Engström, Åke ; Strømgaard, Kristian ; Lundström, Patrik ; Ferguson, Neil ; Jemth, Per. / Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 5. pp. 3597-3606.

Bibtex

@article{1b2c6f3199ba4ebfa33ddfb727a3808a,
title = "Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97",
abstract = "The E6 protein of human papillomavirus exhibits complex interaction patterns with several host proteins and their roles in HPV mediated oncogenesis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor suppressor protein SAP97. All potential binding sites in SAP97 bind E6 with micromolar affinity. The dissociation rate constants govern the different affinities of HPV16 and HPV18 E6 for SAP97. Unexpectedly, binding is not mutually exclusive and all three PDZ domains can simultaneously bind E6. Intriguingly, this quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, suggesting that a conformational change occurs in the PDZ region upon binding, a conclusion supported by kinetic experiments. Using NMR, we discovered a new mode of interaction between E6 and PDZ: a subset of residues distal to the canonical binding pocket in the PDZ2 domain exhibited non-canonical interactions with the E6 protein. This is consistent with a larger proportion of the protein surface defining binding specificity, as compared to that previously reported.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Chi, {Celestine Ngang} and Anders Bach and {\AA}ke Engstr{\"o}m and Kristian Str{\o}mgaard and Patrik Lundstr{\"o}m and Neil Ferguson and Per Jemth",
year = "2011",
month = "2",
day = "4",
doi = "10.1074/jbc.M110.190264",
language = "English",
volume = "286",
pages = "3597--3606",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Biophysical characterization of the complex between human papillomavirus E6 protein and synapse-associated protein 97

AU - Chi, Celestine Ngang

AU - Bach, Anders

AU - Engström, Åke

AU - Strømgaard, Kristian

AU - Lundström, Patrik

AU - Ferguson, Neil

AU - Jemth, Per

PY - 2011/2/4

Y1 - 2011/2/4

N2 - The E6 protein of human papillomavirus exhibits complex interaction patterns with several host proteins and their roles in HPV mediated oncogenesis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor suppressor protein SAP97. All potential binding sites in SAP97 bind E6 with micromolar affinity. The dissociation rate constants govern the different affinities of HPV16 and HPV18 E6 for SAP97. Unexpectedly, binding is not mutually exclusive and all three PDZ domains can simultaneously bind E6. Intriguingly, this quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, suggesting that a conformational change occurs in the PDZ region upon binding, a conclusion supported by kinetic experiments. Using NMR, we discovered a new mode of interaction between E6 and PDZ: a subset of residues distal to the canonical binding pocket in the PDZ2 domain exhibited non-canonical interactions with the E6 protein. This is consistent with a larger proportion of the protein surface defining binding specificity, as compared to that previously reported.

AB - The E6 protein of human papillomavirus exhibits complex interaction patterns with several host proteins and their roles in HPV mediated oncogenesis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor suppressor protein SAP97. All potential binding sites in SAP97 bind E6 with micromolar affinity. The dissociation rate constants govern the different affinities of HPV16 and HPV18 E6 for SAP97. Unexpectedly, binding is not mutually exclusive and all three PDZ domains can simultaneously bind E6. Intriguingly, this quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, suggesting that a conformational change occurs in the PDZ region upon binding, a conclusion supported by kinetic experiments. Using NMR, we discovered a new mode of interaction between E6 and PDZ: a subset of residues distal to the canonical binding pocket in the PDZ2 domain exhibited non-canonical interactions with the E6 protein. This is consistent with a larger proportion of the protein surface defining binding specificity, as compared to that previously reported.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1074/jbc.M110.190264

DO - 10.1074/jbc.M110.190264

M3 - Journal article

C2 - 21113079

VL - 286

SP - 3597

EP - 3606

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

ER -

ID: 32320949