Insights into the potential function and membrane organization of the TP0435 (Tp17) lipoprotein from Treponema pallidum derived from structural and biophysical analyses

The sexually transmitted disease syphilis is caused by the bacterial spirochete Treponema pallidum. This microorganism is genetically intractable, accounting for the large number of putative and undercharacterized members of the pathogen's proteome. In an effort to ascribe a function(s) to the...

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Bibliographic Details
Published in:Protein science 2015-01, Vol.24 (1), p.11-19
Main Authors: Brautigam, Chad A., Deka, Ranjit K., Liu, Wei Z., Norgard, Michael V.
Format: Article
Language:English
Subjects:
Antigens, Bacterial - chemistry
Antigens, Bacterial - genetics
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
beta‐barrel protein
Crystallography, X-Ray
disulfide‐linked dimer
lipoprotein
Lipoproteins - chemistry
Lipoproteins - genetics
Models, Molecular
Mutagenesis, Site-Directed
Protein Conformation
Protein Multimerization
Syphilis - microbiology
Treponema pallidum
Treponema pallidum - chemistry
Treponema pallidum - genetics
X‐ray crystallography
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Summary:The sexually transmitted disease syphilis is caused by the bacterial spirochete Treponema pallidum. This microorganism is genetically intractable, accounting for the large number of putative and undercharacterized members of the pathogen's proteome. In an effort to ascribe a function(s) to the TP0435 (Tp17) lipoprotein, we engineered a soluble variant of the protein (rTP0435) and determined its crystal structure at a resolution of 2.42 Å. The structure is characterized by an eight‐stranded β‐barrel protein with a shallow “basin” at one end of the barrel and an α‐helix stacked on the opposite end. Furthermore, there is a disulfide‐linked dimer of the protein in the asymmetric unit of the crystals. Solution hydrodynamic experiments established that purified rTP0435 is monomeric, but specifically forms the disulfide‐stabilized dimer observed in the crystal structure. The data herein, when considered with previous work on TP0435, imply plausible roles for the protein in either ligand binding, treponemal membrane architecture, and/or pathogenesis. 4U3Q
ISSN:0961-8368
1469-896X
DOI:10.1002/pro.2576