4IZL

Structure Of The N248A Mutant of the PANTON-VALENTINE LEUCOCIDIN S Component from STAPHYLOCOCCUS AUREUS

Summary for 4IZL

• Entry DOI: 10.2210/pdb4izl/pdb
• Related: 1PVL 1T5R 4IYA 4IYC 4IYT 4J0O
• Descriptor: LukS-PV (2 entities in total)
• Functional Keywords: bi-component leucotoxin, staphylococcus aureus, s component leucocidin, beta-barrel pore forming toxin, toxin
• Biological source: Staphylococcus phage PVL
• Total number of polymer chains: 4
• Total formula weight: 132389.78

Authors

Maveyraud, L.,Laventie, B.J.,Prevost, G.,Mourey, L. (deposition date: 2013-01-30, release date: 2014-01-29, Last modification date: 2023-11-08)

Primary citation

Laventie, B.J.,Guerin, F.,Mourey, L.,Tawk, M.Y.,Jover, E.,Maveyraud, L.,Prevost, G.
Residues essential for panton-valentine leukocidin s component binding to its cell receptor suggest both plasticity and adaptability in its interaction surface
Plos One, 9:e92094-e92094, 2014

PubMed Abstract: Panton-Valentine leukocidin (PVL), a bicomponent staphylococcal leukotoxin, is involved in the poor prognosis of necrotizing pneumonia. The present study aimed to elucidate the binding mechanism of PVL and in particular its cell-binding domain. The class S component of PVL, LukS-PV, is known to ensure cell targeting and exhibits the highest affinity for the neutrophil membrane (Kd∼10(-10) M) compared to the class F component of PVL, LukF-PV (Kd∼10(-9) M). Alanine scanning mutagenesis was used to identify the residues involved in LukS-PV binding to the neutrophil surface. Nineteen single alanine mutations were performed in the rim domain previously described as implicated in cell membrane interactions. Positions were chosen in order to replace polar or exposed charged residues and according to conservation between leukotoxin class S components. Characterization studies enabled to identify a cluster of residues essential for LukS-PV binding, localized on two loops of the rim domain. The mutations R73A, Y184A, T244A, H245A and Y250A led to dramatically reduced binding affinities for both human leukocytes and undifferentiated U937 cells expressing the C5a receptor. The three-dimensional structure of five of the mutants was determined using X-ray crystallography. Structure analysis identified residues Y184 and Y250 as crucial in providing structural flexibility in the receptor-binding domain of LukS-PV.

PubMed: 24643034
DOI: 10.1371/journal.pone.0092094

Experimental method

X-RAY DIFFRACTION (2.8 Å)