English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/3577
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Citado 31 veces en Web of Knowledge®  |  Pub MebCentral Ver citas en PubMed Central  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar otros formatos: Exportar EndNote (RIS)Exportar EndNote (RIS)Exportar EndNote (RIS)
Título : Conformation and concerted dynamics of the integrin-binding site and the C-terminal region of echistatin revealed by homonuclear NMR
Autor : Monleón, Daniel; Esteve, Vicent; Kovacs, Helena; Calvete, Juan J. ; Celda, Bernardo
Palabras clave : RGD disintegrin
Echistatin, integrin
NMR protein dynamics determination
Off-resonance rotating-frame Overhauser enhancement spectroscopy (off-resonance ROESY)
Fecha de publicación : 22-mar-2005
Editor: Biochemical Society
Citación : Biochem J. 2005 April 1; 387(Pt 1): 57–66
Resumen: Echistatin is a potent antagonist of the integrins αvβ3, α5β1 and αIIbβ3. Its full inhibitory activity depends on an RGD (Arg-Gly-Asp) motif expressed at the tip of the integrin-binding loop and on its C-terminal tail. Previous NMR structures of echistatin showed a poorly defined integrin-recognition sequence and an incomplete C-terminal tail, which left the molecular basis of the functional synergy between the RGD loop and the C-terminal region unresolved. We report a high-resolution structure of echistatin and an analysis of its internal motions by off-resonance ROESY (rotating-frame Overhauser enhancement spectroscopy). The full-length C-terminal polypeptide is visible as a β-hairpin running parallel to the RGD loop and exposing at the tip residues Pro43, His44 and Lys45. The side chains of the amino acids of the RGD motif have well-defined conformations. The integrin-binding loop displays an overall movement with maximal amplitude of 30°. Internal angular motions in the 100–300 ps timescale indicate increased flexibility for the backbone atoms at the base of the integrin-recognition loop. In addition, backbone atoms of the amino acids Ala23 (flanking the R24GD26 tripeptide) and Asp26 of the integrin-binding motif showed increased angular mobility, suggesting the existence of major and minor hinge effects at the base and the tip, respectively, of the RGD loop. A strong network of NOEs (nuclear Overhauser effects) between residues of the RGD loop and the C-terminal tail indicate concerted motions between these two functional regions. A full-length echistatin–αvβ3 docking model suggests that echistatin's C-terminal amino acids may contact αv-subunit residues and provides new insights to delineate structure–function correlations.
Descripción : Copyright © by Portland Press. The final version of record is available at http://www.biochemj.org/bj/default.htm
URI : http://hdl.handle.net/10261/3577
DOI: 10.1042/BJ20041343
ISSN: 1470-8728
Aparece en las colecciones: (IBV) Artículos
Ficheros en este ítem:
No hay ficheros asociados a este ítem.
Mostrar el registro completo
 



NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.