Crystal structure of the Drosophila peptidoglycan recognition protein (PGRP)-SA at 1.56 A resolution.
Peptidoglycan recognition proteins (PGRPs) form a recently discovered protein family, which is conserved from insect to mammals and is implicated in the innate immune system by interacting with/or degrading microbial peptidoglycans (PGNs). Drosophila PGRP-SA is a member of this family of pattern recognition receptors and is involved in insect Toll activation. We report here the crystal structure of PGRP-SA at 1.56 A resolution, which represents the first example of a "recognition" PGRP. Comparison with the catalytic Drosophila PGRP-LB reveals an overall structure conservation with an L-shaped hydrophilic groove that is likely the PGN carbohydrate core binding site, but further suggests some possible functional homology between recognition and catalytic PGRPs. Consistent with sequence analysis, PGRP-SA does not contain the canonical zinc-binding residues found in catalytic PGRPs. However, substitution of the zinc-binding cysteine residue by serine, along with an altered coordinating histidine residue, assembles a constellation of residues that resembles a modified catalytic triad. The serine/histidine juxtaposition to a threonine residue and a carbonyl oxygen atom, along with conservation of the catalytic water molecule found in PGRP-LB, tantalizingly suggests some hydrolytic function for this member of receptor PGRPs.
Reiser
Jean-Baptiste
JB
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla CA 92037, USA.
Teyton
Luc
L
Wilson
Ian A
IA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004330:Drosophila / Q000737:chemistry*; D029721:Drosophila Proteins / Q000737:chemistry*; D006639:Histidine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010100:Oxygen / Q000737:chemistry; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D002352:Carrier Proteins; D029721:Drosophila Proteins; C118897:peptidoglycan recognition protein; D014867:Water; D012694:Serine; D006639:Histidine; D010100:Oxygen