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La estructura cristalina de ICAM-2 revela una superficie distintiva de reconocimiento de integrinas
J M Casasnovas1, T A Springer, J H Liu
1The Center for Blood Research, Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA.
Nature
|May 15, 1997
Resumen
La estructura cristalina de la molécula de adhesión intercelular-2 (ICAM-2) revela diferencias clave en la forma en que las integrinas con y sin.
Área de la Ciencia:
- La adhesión celular es la adhesión celular.
- Biología estructural Biología estructural.
- Inmunología Inmunología.
Sus antecedentes:
- Las proteínas integrinas median las interacciones de la matriz célula-célula y célula-extracelular.
- Las estructuras conocidas de ligandos de integrinas (fibronectina, VCAM-1) involucran integrinas que carecen de dominios "I".
- Las moléculas de adhesión intercelular (ICAM) son reconocidas por integrinas que contienen el dominio "I" como el antígeno 1 asociado a la función linfocítica (LFA-1).
Objetivo del estudio:
- Determinar la estructura cristalina de la región extracelular del ICAM-2.
- Para aclarar la base estructural para el reconocimiento LFA-1 de ICAM-2.
- Para comparar las arquitecturas de reconocimiento de sitios entre las interacciones integrina-ligando que contienen dominio "I" y las que carecen de dominio "I".
Principales métodos:
- Cristalografía de rayos X para determinar la estructura tridimensional del ICAM-2.
- Análisis estructural para identificar los principales residuos y características involucradas en la unión de LFA-1.
- Modelado estructural comparativo del ICAM-1 basado en la estructura del ICAM-2.
Principales resultados:
- Se determinó la estructura cristalina de la región extracelular de ICAM-2.
- El ácido glutámico en la posición 37 (Glu 37) en ICAM-2 es crítico para la unión de LFA-1 y puede coordinar el ion Mg2+ en el dominio "I" de LFA-1.
- ICAM-2 presenta una superficie de reconocimiento relativamente plana con Glu 37 en una hebra beta, en contraste con los bucles sobresalientes en la fibronectina y VCAM-1.
Conclusiones:
- Existen diferencias estructurales en los sitios de reconocimiento entre integrinas con y sin dominios "I".
- Una curva entre los dominios ICAM-2 y los glicanos ligados a N puede facilitar la unión de LFA-1.
- La estructura de ICAM-2 proporciona un modelo para comprender el reconocimiento de ICAM-1 y las posibles interacciones de patógenos.
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