 |
PDBsum entry 2o6c
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Membrane protein, protein binding
|
PDB id
|
|
|
|
2o6c
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of the tp34 (tp0971) lipoprotein of treponema pallidum: implications of its metal-Bound state and affinity for human lactoferrin.
|
|
|
Authors
|
|
R.K.Deka,
C.A.Brautigam,
F.L.Tomson,
S.B.Lumpkins,
D.R.Tomchick,
M.Machius,
M.V.Norgard.
|
|
|
Ref.
|
|
J Biol Chem, 2007,
282,
5944-5958.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
