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A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing
Published on: July 3, 2016
La inestabilidad, el despliegue y la agregación de las variantes de lisozima humana subyacentes a la fibrilogénesis
D R Booth1, M Sunde, V Bellotti
1Immunological Medicine Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Nature
|February 27, 1997
Resumen
Las variantes humanas de la lisozima son inestables y forman fibrillas amiloides. Este proceso de plegamiento incorrecto de proteínas, que involucra intermedios parcialmente plegados, es relevante para las enfermedades de amiloidosis.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
Sus antecedentes:
- Las fibrillas amiloides, formadas por mal plegamiento y agregación de proteínas, están implicadas en enfermedades mortales.
- La lisozima humana, una proteína natural, existe en dos variantes que se sabe que son amiloidogénicas.
Objetivo del estudio:
- Investigar las propiedades de estabilidad y agregación de las variantes humanas de lisozima.
- Para dilucidar la transformación estructural durante la formación de fibrillas amiloides por la lisozima humana.
Principales métodos:
- Cristalografía de rayos X para determinar el pliegue nativo de las proteínas.
- Estudios biofísicos para analizar la estabilidad de las proteínas y las vías de agregación.
- Análisis estructural de la formación de fibrillas amiloides.
Principales resultados:
- Se encontró que ambas variantes de lisozima humana eran inestables.
- Las fibrillas amiloides se formaron a través de la transformación del pliegue helicoidal nativo en un pliegue beta cruzado.
- Se identificaron productos intermedios parcialmente plegados como potencialmente involucrados en el proceso de agregación.
Conclusiones:
- La inestabilidad de las variantes humanas de la lisozima contribuye a su naturaleza amiloidógena.
- La transición estructural del pliegue helicoidal al pliegue beta cruzado es un evento clave en la fibrilogénesis de la lisozima.
- Comprender estos mecanismos puede ofrecer información sobre la patogénesis de la amiloidosis.
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