PDBsum entry 2o6c

Membrane protein, protein binding

PDB id: 2o6c

Contents

Protein chains

158 a.a. *

Ligands

EDO ×2

SO4 ×2

Metals

_CL ×4

Waters ×221

* Residue conservation analysis

PDB id:

2o6c

Name:

Membrane protein, protein binding

Title:

Structure of selenomethionyl rtp34 from treponema pallidum

Structure:

34 kda membrane antigen. Chain: a, b. Synonym: pathogen-specific membrane antigen. Engineered: yes. Mutation: yes

Source:

Treponema pallidum. Organism_taxid: 160. Gene: tpd. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.70Å R-factor: 0.187 R-free: 0.215

Authors:

M.Machius,C.A.Brautigam,R.K.Deka,D.R.Tomchick,S.B.Lumpkins, M.V.Norgard

Key ref:

R.K.Deka et al. (2007). Crystal structure of the Tp34 (TP0971) lipoprotein of treponema pallidum: implications of its metal-bound state and affinity for human lactoferrin. J Biol Chem, 282, 5944-5958. PubMed id: 17192261 DOI: 10.1074/jbc.M610215200

Date:

07-Dec-06 Release date: 26-Dec-06

Protein chains

P19478  (TA34_TREPA) -  34 kDa membrane antigen from Treponema pallidum (strain Nichols)

Seq: 204 a.a.

Struc: 158 a.a.

DOI no: 10.1074/jbc.M610215200

J Biol Chem 282:5944-5958 (2007)

PubMed id: 17192261

Crystal structure of the Tp34 (TP0971) lipoprotein of treponema pallidum: implications of its metal-bound state and affinity for human lactoferrin.

R.K.Deka, C.A.Brautigam, F.L.Tomson, S.B.Lumpkins, D.R.Tomchick, M.Machius, M.V.Norgard.

ABSTRACT

The Tp34 (TP0971) membrane lipoprotein of Treponema pallidum, an obligate human pathogen and the agent of syphilis, was previously reported to have lactoferrin binding properties. Given the non-cultivatable nature of T. pallidum, a structure-to-function approach was pursued to clarify further potential relationships between the Tp34 structural and biochemical properties and its propensity to bind human lactoferrin. The crystal structure of a nonacylated, recombinant form of Tp34 (rTp34), solved to a resolution of 1.9A(,) revealed two metaloccupied binding sites within a dimer; the identity of the ion most likely was zinc. Residues from both of the monomers contributed to the interfacial metal-binding sites; a novel feature was that the delta-sulfur of methionine coordinated the zinc ion. Analytical ultracentrifugation showed that, in solution, rTp34 formed a metal-stabilized dimer and that rTp34 bound human lactoferrin with a stoichiometry of 2:1. Isothermal titration calorimetry further revealed that rTp34 bound human lactoferrin at high (submicromolar) affinity. Finally, membrane topology studies revealed that native Tp34 is not located on the outer surface (outer membrane) of T. pallidum but, rather, is periplasmic. How propensity of Tp34 to bind zinc and the iron-sequestering lactoferrin may relate overall to the biology of T. pallidum infection in humans is discussed.

Selected figure(s)

Figure 1.
FIGURE 1. The crystal structure of rTp34. A, monomeric structure. A ribbon model of the crystal structure is shown with secondary structural elements colored purple for -strands, green for the 3[10] helix, and blue for regions with no regular secondary structure. Letters of the elements are indicated, as are the N and C termini of the model. B, dimeric structure. The bottom monomer is colored as in A and is rotated about 90° to the left around the vertical axis. The other monomer is colored tan. Residues that form inner-sphere contacts with the two interdimeric Zn^2+ ions (orange spheres) are shown as balls and sticks and are colored according to the monomer from which they originate; purple for the bottom monomer, and tan for the top. The liganding interactions are shown as black dashed lines.

Figure 6.
FIGURE 6. Superposition of IL2R D1 to rTp34. A stereo diagram of a smoothed trace through the C[ ]atoms of IL2R D1 (blue) and rTp34 (red) is shown. The orientation of rTp34 is similar to that shown in Fig. 1A.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 5944-5958) copyright 2007.

Figures were selected by an automated process.