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Understanding the role of phosphorylation in the binding mechanism of a PDZ domain
Sapienza Univ Roma, Dipartimento Sci Biochim A Rossi Fanelli, Fdn Cenci Bolognetti, Ist Pasteur,Ist Biol & Patol Mol,CNR, Ple A Moro 5, I-00185 Rome, Italy..
Sapienza Univ Roma, Dipartimento Sci Biochim A Rossi Fanelli, Fdn Cenci Bolognetti, Ist Pasteur,Ist Biol & Patol Mol,CNR, Ple A Moro 5, I-00185 Rome, Italy..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Sapienza Univ Roma, Dipartimento Sci Biochim A Rossi Fanelli, Fdn Cenci Bolognetti, Ist Pasteur,Ist Biol & Patol Mol,CNR, Ple A Moro 5, I-00185 Rome, Italy..
2017 (English)In: Protein Engineering Design & Selection, ISSN 1741-0126, E-ISSN 1741-0134, Vol. 30, no 1, 1-5 p.Article in journal (Refereed) Published
Abstract [en]

The PDZ domain is one of the most common protein-protein interaction domains in mammalian species. While several studies have demonstrated the importance of phosphorylation in interactions involving PDZ domains, there is a paucity of detailed mechanistic data addressing how the PDZ interaction is affected by phosphorylation. Here, we address this question by equilibrium and kinetic binding experiments using PDZ2 from protein tyrosine phosphatase L1 and its interaction with a peptide from the natural ligand RIL. The results show that phosphorylation of a serine residue in the RIL peptide has dual and opposing effects: it increases both the association and dissociation rate constants, which leads to an overall weakening of binding. Furthermore, we performed binding experiments with a RIL peptide in which the serine was replaced by a glutamate, a commonly used method to mimic phosphorylation in proteins. Strikingly, both the affinity and the ionic strength dependence of the affinity differed markedly for the phosphoserine and glutamate peptides. These results show that, in this particular case, glutamate is a poor mimic of serine phosphorylation.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2017. Vol. 30, no 1, 1-5 p.
Keyword [en]
ionic strength, kinetics, peptide binding, protein-protein interaction
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-319870DOI: 10.1093/protein/gzw055ISI: 000397129400001PubMedID: 27760803OAI: oai:DiVA.org:uu-319870DiVA: diva2:1088630
Funder
Swedish Research Council
Available from: 2017-04-13 Created: 2017-04-13 Last updated: 2017-04-13Bibliographically approved

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