Probing solution structure of the pentameric ligand-gated ion channel GLIC by small-angle neutron scattering.
Proc Natl Acad Sci U S A
; 118(37)2021 09 14.
Article
em En
| MEDLINE
| ID: mdl-34504004
ABSTRACT
Pentameric ligand-gated ion channels undergo subtle conformational cycling to control electrochemical signal transduction in many kingdoms of life. Several crystal structures have now been reported in this family, but the functional relevance of such models remains unclear. Here, we used small-angle neutron scattering (SANS) to probe ambient solution-phase properties of the pH-gated bacterial ion channel GLIC under resting and activating conditions. Data collection was optimized by inline paused-flow size-exclusion chromatography, and exchanging into deuterated detergent to hide the micelle contribution. Resting-state GLIC was the best-fit crystal structure to SANS curves, with no evidence for divergent mechanisms. Moreover, enhanced-sampling molecular-dynamics simulations enabled differential modeling in resting versus activating conditions, with the latter corresponding to an intermediate ensemble of both the extracellular and transmembrane domains. This work demonstrates state-dependent changes in a pentameric ion channel by SANS, an increasingly accessible method for macromolecular characterization with the coming generation of neutron sources.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Ativação do Canal Iônico
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Estrutura Quaternária de Proteína
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Espalhamento a Baixo Ângulo
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Multimerização Proteica
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Canais Iônicos de Abertura Ativada por Ligante
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Nêutrons
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article