title: Crystal structure of lipoprotein GNA1946 from Neisseria meningitidis.
abstract: GNA1946, a conserved outer membrane lipoprotein from Neisseria meningitidis, has been identified as a candidate antigen for an urgently needed broad-spectrum meningococcal vaccine. It has been predicted to be a periplasmic receptor in the D-methionine uptake ABC transporter system. The crystal structure of GNA1946 was solved by the single-wavelength anomalous dispersion (SAD) method to a resolution of 2.25 A, and it reveals a Venus flytrap-like structure. GNA1946 consists of two globular lobes connected by a hinge region. Surprisingly, the structure showed an L-methionine bound within the cleft between the lobes. A comparison of GNA1946 with two other outer membrane lipoproteins, the L-methionine-binding Tp32 from Treponema pallidum and the dipeptide GlyMet-binding protein Pg110 from Staphylococcus aureus, revealed that although these three proteins share low sequence similarities, there is a high degree of structural conservation and similar substrate-binding frameworks. Our results reveal that GNA1946 is an L-methionine binding lipoprotein in the outer membrane, and should function as an initial receptor for ABC transporters with high affinity and specificity. The GNA1946 structure reported here should provide a valuable starting point for the development of a broad-spectrum meningococcal vaccine.
authors.affiliation: Tianjin Key Laboratory of Protein Science, The College of Life Science, Nankai University, Tianjin, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wu
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Wang
authors.forename: Chunting
authors.initials: C
authors.lastname: Yang
authors.forename: Honglin
authors.initials: H
authors.lastname: Xu
authors.forename: Yuequan
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008074:Lipoproteins