Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates.
The complement system is an essential component of the innate and acquired immune system, and consists of a series of proteolytic cascades that are initiated by the presence of microorganisms. In health, activation of complement is precisely controlled through membrane-bound and soluble plasma-regulatory proteins including complement factor H (fH; ref. 2), a 155 kDa protein composed of 20 domains (termed complement control protein repeats). Many pathogens have evolved the ability to avoid immune-killing by recruiting host complement regulators and several pathogens have adapted to avoid complement-mediated killing by sequestering fH to their surface. Here we present the structure of a complement regulator in complex with its pathogen surface-protein ligand. This reveals how the important human pathogen Neisseria meningitidis subverts immune responses by mimicking the host, using protein instead of charged-carbohydrate chemistry to recruit the host complement regulator, fH. The structure also indicates the molecular basis of the host-specificity of the interaction between fH and the meningococcus, and informs attempts to develop novel therapeutics and vaccines.
Schneider
Muriel C
MC
Centre for Molecular Microbiology and Infection, Imperial College, London SW7 2AZ, UK.
Prosser
Beverly E
BE
Caesar
Joseph J E
JJ
Kugelberg
Elisabeth
E
Li
Su
S
Zhang
Qian
Q
Quoraishi
Sadik
S
Lovett
Janet E
JE
Deane
Janet E
JE
Sim
Robert B
RB
Roversi
Pietro
P
Johnson
Steven
S
Tang
Christoph M
CM
Lea
Susan M
SM
D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D017242:Complement Factor H / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D018716:Molecular Mimicry; D009345:Neisseria meningitidis / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002241:Carbohydrates; D008024:Ligands; C484699:factor H-binding protein, Neisseria meningitidis; D017242:Complement Factor H