Real-time observation of ligand-induced allosteric transitions in a PDZ domain.
Proc Natl Acad Sci U S A
; 117(42): 26031-26039, 2020 10 20.
Article
em En
| MEDLINE
| ID: mdl-33020277
ABSTRACT
While allostery is of paramount importance for protein regulation, the underlying dynamical process of ligand (un)binding at one site, resulting time evolution of the protein structure, and change of the binding affinity at a remote site are not well understood. Here the ligand-induced conformational transition in a widely studied model system of allostery, the PDZ2 domain, is investigated by transient infrared spectroscopy accompanied by molecular dynamics simulations. To this end, an azobenzene-derived photoswitch is linked to a peptide ligand in a way that its binding affinity to the PDZ2 domain changes upon switching, thus initiating an allosteric transition in the PDZ2 domain protein. The subsequent response of the protein, covering four decades of time, ranging from â¼1 ns to â¼µs, can be rationalized by a remodeling of its rugged free-energy landscape, with very subtle shifts in the populations of a small number of structurally well-defined states. It is proposed that structurally and dynamically driven allostery, often discussed as limiting scenarios of allosteric communication, actually go hand-in-hand, allowing the protein to adapt its free-energy landscape to incoming signals.
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Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
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Proteínas Tirosina Fosfatases
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Domínios PDZ
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Simulação de Dinâmica Molecular
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
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