Selective recognition of synthetic lysine and meso-diaminopimelic acid-type peptidoglycan fragments by human peptidoglycan recognition proteins I{alpha} and S.
The interactions of a range of synthetic peptidoglycan derivatives with PGRP-Ialpha and PGRP-S have been studied in real-time using surface plasmon resonance. A dissociation constant of K(D) = 62 mum was obtained for the interaction of peptidoglycan recognition protein (PGRP)-Ialpha with the lysine-containing muramyl pentapeptide (compound 6). The normalized data for the lysine-containing muramyl tetra- (compound 5) and pentapeptide (compound 6) showed that these compounds have similar affinities, whereas a much lower affinity for muramyl tripeptide (compound 3) was measured. Similar affinities were obtained when the lysine moiety of the muramyl peptides was replaced by meso-diaminopimelic acid (DAP). Furthermore, the compounds that contained only a stem peptide (pentapeptide, compound 1) and (DAP-PP, compound 2) as well as muramyldipeptide (compound 3) exhibited no binding indicating that the muramyltripeptide (compound 4) is the smallest peptidoglycan fragment that can be recognized by PGRP-Ialpha. Surprisingly, PGRP-S derived significantly higher affinities for the DAP-containing fragments to similar lysine-containing derivatives, and the following dissociation constants were measured: muramylpentapeptide-DAP, K(D) = 104 nm; muramyltetrapeptide-DAP, 92.4 nm; and muramyltripeptide-DAP, 326 nm. The binding profiles were rationalized by using a recently reported x-ray crystal structure of PGRP-Ialpha with the lysine-containing muramyltripeptide (4).
Kumar
Sanjay
S
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.
Roychowdhury
Abhijit
A
Ember
Brian
B
Wang
Qian
Q
Guan
Rongjin
R
Mariuzza
Roy A
RA
Boons
Geert-Jan
GJ
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000737:chemistry; D016207:Cytokines / Q000737:chemistry* / Q000378:metabolism*; D003960:Diaminopimelic Acid / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms; D020349:Surface Plasmon Resonance
D016207:Cytokines; D008024:Ligands; C491878:PGLYRP1 protein, human; D010446:Peptide Fragments; D010457:Peptidoglycan; D020033:Protein Isoforms; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; C035104:muramylNAc-Ala-isoGln-Lys-tripeptide; D008239:Lysine