PDBsum entry 2kc0

Protein binding

PDB id: 2kc0

Contents

Protein chain

242 a.a. *

* Residue conservation analysis

PDB id:

2kc0

Name:

Protein binding

Title:

Solution structure of the factor h binding protein

Structure:

Lipoprotein. Chain: a. Fragment: unp residues 8-255. Synonym: factor h binding protein variant b24_002. Engineered: yes

Source:

Neisseria meningitidis. Organism_taxid: 487. Gene: nmb1870. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

25 models

Authors:

F.Cantini,D.Veggi,S.Dragonetti,S.Savino,M.Scarselli,G.Romagnoli, M.Pizza,L.Banci,R.Rappuoli

Key ref:

F.Cantini et al. (2009). Solution Structure of the Factor H-binding Protein, a Survival Factor and Protective Antigen of Neisseria meningitidis. J Biol Chem, 284, 9022-9026. PubMed id: 19196709 DOI: 10.1074/jbc.C800214200

Date:

13-Dec-08 Release date: 17-Feb-09

Protein chain

Q6QCC2  (Q6QCC2_NEIME) -  Factor H-binding protein from Neisseria meningitidis

Seq: 274 a.a.

Struc: 242 a.a.

DOI no: 10.1074/jbc.C800214200

J Biol Chem 284:9022-9026 (2009)

PubMed id: 19196709

Solution Structure of the Factor H-binding Protein, a Survival Factor and Protective Antigen of Neisseria meningitidis.

F.Cantini, D.Veggi, S.Dragonetti, S.Savino, M.Scarselli, G.Romagnoli, M.Pizza, L.Banci, R.Rappuoli.

ABSTRACT

Factor H-binding protein is a 27-kDa lipoprotein of Neisseria meningitidis discovered while screening the bacterial genome for vaccine candidates. In addition to being an important component of a vaccine against meningococcus in late stage of development, the protein is essential for pathogenesis because it allows the bacterium to survive and grow in human blood by binding the human complement factor H. We recently reported the solution structure of the C-terminal domain of factor H-binding protein, which contains the immunodominant epitopes. In the present study, we report the structure of the full-length molecule, determined by nuclear magnetic resonance spectroscopy. The protein is composed of two independent barrels connected by a short link. Mapping the residues recognized by monoclonal antibodies with bactericidal or factor H binding inhibition properties allowed us to predict the sites involved in the function of the protein. The structure therefore provides the basis for designing improved vaccine molecules.

Selected figure(s)

Figure 1.
A, topology diagram of the fHbp protein. The α-helices are represented by sky blue cylinders, and the β-strands are cyan arrows. N-term, N terminus; C-term, C terminus. B, ribbon diagram of fHbp. Secondary structure elements are shown. β-strands of the N-terminal domain are shown in cyan and helices are shown in red, whereas β-strands of fHbpC are shown in blue. C, the side chains of the hydrophobic residues involved in interdomains contacts are shown as sticks in red, and pink. Contact surfaces are also reported. The other hydrophobic residues are shown in blue. The charged residues are shown in green. The backbone is shown as a ribbon.

Figure 2.
A, variability profile of the three fHbp variants. Conserved amino acids are colored in blue, conservative substitutions are colored in gray, and variable amino acids are colored in green. B, distribution of amino acids recognized by monoclonal antibodies (Mabs) raised against v.1 (purple) and v.2/v.3 (green). C and D, molecular areas recognized by the bactericidal pairs of monoclonal antibodies against v.1 (orange) and v.2 (gold) (11). E, molecular distribution of fHbp residues recognized by monoclonal antibodies inhibiting (red), partially inhibiting (orange), and not inhibiting (green) the fH binding (11).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 9022-9026) copyright 2009.