Functional clues from the crystal structure of an orphan periplasmic ligand‐binding protein from Treponema pallidum

Abstract

The spirochete Treponema pallidum is the causative agent of syphilis, a sexually transmitted infection of major global importance. Other closely related subspecies of Treponema also are the etiological agents of the endemic treponematoses, such as yaws, pinta, and bejel. The inability of T. pallidum and its close relatives to be cultured in vitro has prompted efforts to characterize T. pallidum's proteins structurally and biophysically, particularly those potentially relevant to treponemal membrane biology, with the goal of possibly revealing the functions of those proteins. This report describes the structure of the treponemal protein Tp0737; this polypeptide has a fold characteristic of a class of periplasmic ligand-binding proteins associated with ABC-type transporters. Although no ligand for the protein was observed in electron-density maps, and thus the nature of the native ligand remains obscure, the structural data described herein provide a foundation for further efforts to elucidate the ligand and thus the function of this protein in T. pallidum.

Biophysical and Biochemical Characterization of TP0037, a d -Lactate Dehydrogenase, Supports an Acetogenic Energy Conservation Pathway in Treponema pallidum

“…As an approach to circumvent historic research barriers and to elucidate previously unappreciated molecular and mechanistic features of T. pallidum , we have focused on discerning salient structure-function relationships for T. pallidum ’s membrane lipoproteins (LPs) ( 7 , 17 – 31 ). Membrane LPs serve many key functions in pathogenic bacteria ( 32 , 33 ), and numerous studies point to the importance of LPs in crucial aspects of T. pallidum biology (about 4.4% of T. pallidum ’s genome encodes 48 or more LPs) ( 34 , 35 ).…”

“…Membrane LPs serve many key functions in pathogenic bacteria ( 32 , 33 ), and numerous studies point to the importance of LPs in crucial aspects of T. pallidum biology (about 4.4% of T. pallidum ’s genome encodes 48 or more LPs) ( 34 , 35 ). Our discovery-driven approach has involved characterizing recombinant versions of the treponemal LPs using structural biology, protein biophysics, and biochemistry ( 17 – 31 , 36 ). These efforts have led to a number of novel discoveries for T. pallidum ( 17 , 21 – 23 , 25 – 28 , 30 ), some of which are applicable to other bacteria ( 22 , 23 , 25 , 27 – 29 , 36 – 39 ).…”

Biophysical insights into a highly selective L-arginine-binding lipoprotein of a pathogenic treponeme

“…Our experiences with the protein suggest that L-arginine is slow to dissociate from Tv2483 in the absence of an external impetus (see above and Experimental Procedures); this aspect of L-arginine binding does not comport with a chemotactic system that must be able to respond rapidly to changes in solute concentrations. Furthermore, the Tp0737 protein of T. pallidum offers an apparent precedent of a treponemal LBP that has no co-operonic ABC transporter apparatus (29).…”

Biophysical insights into a highly selective l‐arginine‐binding lipoprotein of a pathogenic treponeme

“…Our experiences with the protein suggest that l ‐arginine is slow to dissociate from Tv2483 in the absence of an external impetus (see above and Experimental procedures); this aspect of l ‐arginine binding does not comport with a chemotactic system that must be able to respond rapidly to changes in solute concentrations. Furthermore, the Tp0737 protein of T. pallidum offers an apparent precedent of a treponemal LBP that has no co‐operonic ABC transporter apparatus …”