2XXL

Crystal structure of drosophila Grass clip serine protease of Toll pathway

Summary for 2XXL

• Entry DOI: 10.2210/pdb2xxl/pdb
• Descriptor: GRAM-POSITIVE SPECIFIC SERINE PROTEASE, ISOFORM B, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: hydrolase, innate immunity
• Biological source: DROSOPHILA MELANOGASTER
• Total number of polymer chains: 2
• Total formula weight: 92545.49

Authors

Kellenberger, C.,Leone, P.,Coquet, L.,Jouenne, T.,Reichhart, J.M.,Roussel, A. (deposition date: 2010-11-10, release date: 2011-02-09, Last modification date: 2024-10-16)

Primary citation

Kellenberger, C.,Leone, P.,Coquet, L.,Jouenne, T.,Reichhart, J.M.,Roussel, A.
Structure-Function Analysis of Grass Clip Serine Protease Involved in Drosophila Toll Pathway Activation.
J.Biol.Chem., 286:12300-, 2011

PubMed 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.

PubMed: 21310954
DOI: 10.1074/JBC.M110.182741

Experimental method

X-RAY DIFFRACTION (1.8 Å)