4IZL: Structure Of The N248a Mutant Of The Panton-valentine Leucocidin S Component From Staphylococcus Aureus

Citation:
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 approximately 10(-10) M) compared to the class F component of PVL, LukF-PV (Kd approximately 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.
PDB ID: 4IZLDownload
MMDB ID: 117013
PDB Deposition Date: 2013/1/30
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4IZL: monomeric; determined by author and by software (PISA)
Molecular Components in 4IZL
Label Count Molecule
Protein (1 molecule)
1
Luks-pv
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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