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Biochemistry. 2015 Feb 17;54(6):1327-37. doi: 10.1021/bi500845j. Epub 2015 Feb 3.

Disorder-to-order transition of MAGI-1 PDZ1 C-terminal extension upon peptide binding: thermodynamic and dynamic insights.

Author information

1
Equipe Oncoprotéines, Ecole Supérieure de Biotechnologie de Strasbourg, Biotechnologie et Signalisation Cellulaire, UMR 7242, CNRS, Université de Strasbourg , Boulevard Sébastien Brandt, BP 10413, 67412 Illkirch cedex, France.

Abstract

PDZ domains are highly abundant protein-protein interaction modules commonly found in multidomain scaffold proteins. The PDZ1 domain of MAGI-1, a protein present at cellular tight junctions that contains six PDZ domains, is targeted by the E6 oncoprotein of the high-risk human papilloma virus. Thermodynamic and dynamic studies using complementary isothermal titration calorimetry and nuclear magnetic resonance (NMR) (15)N heteronuclear relaxation measurements were conducted at different temperatures to decipher the molecular mechanism of this interaction. Binding of E6 peptides to the MAGI-1 PDZ1 domain is accompanied by an unusually large and negative change in heat capacity (ΔC(p)) that is attributed to a disorder-to-order transition of the C-terminal extension of the PDZ1 domain upon E6 binding. Analysis of temperature-dependent thermodynamic parameters and (15)N NMR relaxation data of a PDZ1 mutant in which this disorder-to-order transition was abolished allows the unusual thermodynamic signature of E6 binding to be correlated to local folding of the PDZ1 C-terminal extension. Comparison of the exchange contributions observed for wild-type and mutant proteins explains how variation in the solvent-exposed area may compensate for the loss of conformational entropy and further designates a distinct set of a few residues that mediate this local folding phenomena.

PMID:
25590897
DOI:
10.1021/bi500845j
[Indexed for MEDLINE]

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