2xxl
Crystal structure of drosophila Grass clip serine protease of Toll pathway
Structural highlights
FunctionGRASS_DROME Endopeptidase (By similarity). Plays a key role in innate immunity by activating the Toll pathway in response to fungal and Gram-positive bacterial infections, presumably downstream of pattern-recognition receptors (PRR), such as PGRP-SA, GNBP1 and GNBP3, and upstream of spz processing enzyme SPE (PubMed:16631589, PubMed:18724373).[UniProtKB:Q9XXV0][1] [2] Publication Abstract from PubMedGrass 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. Structure-function analysis of grass clip serine protease involved in Drosophila Toll pathway activation.,Kellenberger C, Leone P, Coquet L, Jouenne T, Reichhart JM, Roussel A J Biol Chem. 2011 Apr 8;286(14):12300-7. Epub 2011 Feb 10. PMID:21310954[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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