Enlace de la adhesión bacteriana FimH a sus dianas naturales de tipo Glicano de alta mannosa multivalente
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Exploring Protein-Glycan Interactions: Advances in Nuclear Magnetic Resonance
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Maximilian M Sauer1, Roman P Jakob2, Thomas Luber3
1Institute of Molecular Biology & Biophysics , ETH Zurich , Otto-Stern-Weg 5 , CH-8093 Zurich , Switzerland.
Journal of the American Chemical Society
|December 14, 2018
Resumen
La E. coli uropatógena utiliza la FimH para unirse a las células huésped. Este estudio revela cómo FimH interactúa con N-glicanos, ofreciendo ideas para el desarrollo de nuevos medicamentos para bloquear la adhesión bacteriana.
Área de la Ciencia:
- Microbiología
- Biología estructural
- La bioquímica
Sus antecedentes:
- Las interacciones multivalentes entre carbohidratos y lectinas son clave en la adhesión huésped-patógeno.
- Comprender los mecanismos moleculares de adhesión de los patógenos es crucial para el desarrollo de fármacos antimicrobianos.
Objetivo del estudio:
- Caracterizar la interacción entre el FimH de Escherichia coli uropatogénico y los N-glicanos con alto contenido de manosa.
- Para aclarar la base molecular de la adhesión mediada por FimH para el desarrollo de antagonistas.
Principales métodos:
- Determinación de la estructura cristalina de los complejos de FimH-N-glicano.
- Análisis cinético detallado de la unión y disociación de ligandos.
- Investigación de la multimerización y la cooperatividad de la FIMH.
Principales resultados:
- La FimH reconoce los mannosidos α(1-2) - , α(1-3) - y α(1-6) -enlazados terminales con una afinidad similar.
- El estado separado por dominio de FimH exhibe una afinidad 2000 veces mayor que el estado asociado por dominio, independiente del ligando.
- Un solo N-glicano puede unirse a hasta tres moléculas de FimH con cooperatividad negativa.
Conclusiones:
- El estudio proporciona información fundamental sobre los mecanismos de adhesión de la E. coli uropatógena.
- Los hallazgos ofrecen una base sólida para el diseño de antagonistas FimH efectivos para combatir las infecciones.
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