Structure-function analysis of grass clip serine protease involved in Drosophila Toll pathway activation.
J Biol Chem
; 286(14): 12300-7, 2011 Apr 08.
Article
em En
| MEDLINE
| ID: mdl-21310954
ABSTRACT
Grass is a clip domain serine protease (SP) involved in a proteolytic cascade triggering the Toll pathway activation of Drosophila during an immune response. Epistasic studies position it downstream of the apical protease ModSP and upstream of the terminal protease Spaetzle-processing enzyme. Here, we report the crystal structure of Grass zymogen. We found that Grass displays a rather deep active site cleft comparable with that of proteases of coagulation and complement cascades. A key distinctive feature is the presence of an additional loop (75-loop) in the proximity of the activation site localized on a protruding loop. All biochemical attempts to hydrolyze the activation site of Grass failed, strongly suggesting restricted access to this region. The 75-loop is thus proposed to constitute an original mechanism to prevent spontaneous activation. A comparison of Grass with clip serine proteases of known function involved in analogous proteolytic cascades allowed us to define two groups, according to the presence of the 75-loop and the conformation of the clip domain. One group (devoid of the 75-loop) contains penultimate proteases whereas the other contains terminal proteases. Using this classification, Grass appears to be a terminal protease. This result is evaluated according to the genetic data documenting Grass function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Drosophila
/
Receptores Toll-Like
/
Serina Proteases
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article