Lysozyme's lectin-like characteristics facilitates its immune defense function
Rojas-Macias, Miguel A.
Krylov, Vadim B.
Argunov, Dmitry A.
Enani, Mushira Abdelaziz
Scheidig, Axel J.
Nifantiev, Nikolay E.
KAUST Grant NumberKUK-11-008-23
Online Publication Date2017-05-30
Print Publication Date2017
Permanent link to this recordhttp://hdl.handle.net/10754/624958
MetadataShow full item record
AbstractInteractions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.
CitationZhang R, Wu L, Eckert T, Burg-Roderfeld M, Rojas-Macias MA, et al. (2017) Lysozyme’s lectin-like characteristics facilitates its immune defense function. Quarterly Reviews of Biophysics 50. Available: http://dx.doi.org/10.1017/s0033583517000075.
SponsorsThe Swedish NMR Centre is acknowledged for supplying instrument time and support. Diffraction data were collected on a P14 operated by EMBL at the PETRAIII storage ring (Hamburg, Germany). We are grateful to the beamline staff for providing assistance in using the beamline. We thank Dr Timothy Weaver (Cincinnati Children's Hospital Medical Center, Cincinnati, USA) for the provision of human recombinant lysozyme. This work was supported by the King Abdullah University of Science and Technology (grant KUK-11-008-23 awarded to B.N. with a Ph.D. position for L.W.) and the European Research Council (ERC-2008-AdG 227700 to B.N.). Beamtime on the P14 at the EMBL outstation in Hamburg was funded by a BioStruct-X grant. We thank the Sialic Acids Society for financial support. The synthetic portion of the work was supported by the RSF (grant 14-23-00199 to N.E.N.). A.D. would like to thank CSIR, Govt. of India for senior research fellowship.
PublisherCambridge University Press (CUP)
JournalQuarterly Reviews of Biophysics