4C83: Crystal Structure Of The Igg2a Lpt3 In Complex With An 8- Sugar Inner Core Analogue Of Neisseria Meningitidis

Citation:
Abstract
The structure of a antigen-binding fragment (Fab) from the bactericidal monoclonal antibody LPT3-1 specific to lipooligosaccharide (LOS) inner cores from Neisseria meningitidis has been solved in complex with an eight-sugar inner core fragment NmL3 galE lpt3 KOH to 2.69 A resolution. The epitope is centered about an inner core N-acetylglucosamine residue unique to N. meningitidis and does not include the lipid A moiety, which is disordered in the structure, but is positioned to allow the binding of free and membrane-anchored full-length LOS. All the amino acid residues that contact antigen are of germline origin but, remarkably, two consecutive somatic mutations of serine to glycine in the heavy chain at residues 52 and 52a are positioned to deprive the antibody of advantageous interactions and so weaken binding. However, these mutations are key to allowing selective cross-reactivity with the HepII-3-PEtn inner core variant expressed by 70% of strains. Neisseria meningitidis is a leading cause of disease in the developed world and is especially dangerous to children, who lack the necessary protective antibodies. The structure of Fab LPT3-1 in complex with LOS provides insight into the antibody's selective ability to recognize multiple clinically relevant variations of the LOS inner core from N. meningitidis.
PDB ID: 4C83Download
MMDB ID: 117400
PDB Deposition Date: 2013/9/29
Updated in MMDB: 2015/09
Experimental Method:
x-ray diffraction
Resolution: 2.69  Å
Source Organism:
Similar Structures:
Biological Unit for 4C83: dimeric; determined by software (PISA)
Molecular Components in 4C83
Label Count Molecule
Proteins (2 molecules)
1
Lpt3 Light Chain
Molecule annotation
1
Lpt3 Heavy Chain
Molecule annotation
Chemicals (6 molecules)
1
1
2
2
3
1
4
1
5
1
* Click molecule labels to explore molecular sequence information.

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