53 research outputs found
Structural features of PE_PGRS.
(A) A schematic view of the organization of a PE_PGRS protein in PE, linker, and PGRS domain. The conserved GRPLI is highlighted. (B) Stick representation of our previously proposed structural model of a PGRS PGII sandwich domain [4,5]; hydrophobic residues on 1 edge and conserved glycine residues pointing inwards the PGII sandwich are labeled. (C, D) Structural representation of PE_PGRS33 and PE_PGRS35 structures, respectively. PE_PGRS33 PE domain is shown in magenta cartoon, the PGRSs domains in white stick/surface, the PE_PGRS35 catalytic domain in prune cartoon/surface. Hydrophobic residues lining the straight edges of the PGRS33 and PGRS35 domains are colored orange, those of PE_PGRS35 catalytic domain in yellow. (E, F) Two 180° views of electrostatic potential surfaces of PGRS33 and PGRS35, respectively.</p
A speculative drawing of PE_PGRS33 (white), −35 (white-prune), and Wag22 (blue-green) proteins sailing the mycomembrane.
TLR2 (pdb code 6nig) was docked on PGRS33 structure by combining surface complementarity, using the software PatchDock, with refinement of electrostatic interactions and desolvation energy, using FireDock. Structure-based B cell antigen prediction was performed using ElliPro.</p
Predicted functions of PE_PGRS C-terminal domains based on structure alignment.
Z-score and root mean square deviations (RMSD) from most similar structures were computed using DALI. (DOCX)</p
PE_PGRS proteins of <i>Mycobacterium tuberculosis</i>: A specialized molecular task force at the forefront of host–pathogen interaction
To the PE_PGRS protein subfamily belongs a group of surface-exposed mycobacterial antigens that in Mycobacterium tuberculosis (Mtb) H37Rv accounts to more than 65 genes, 51 of which are thought to express a functional protein. PE_PGRS proteins share a conserved structural architecture with three main domains: the N-terminal PE domain; the PGRS domain, that can vary in sequence and size and is characterized by the presence of multiple GGA-GGX amino acid repeats; the highly conserved sequence containing the GRPLI motif that links the PE and PGRS domains; the unique C-terminus end that can vary in size from few to up to ≈ 300 amino acids. pe_pgrs genes emerged in slow-growing mycobacteria and expanded and diversified in MTBC and few other pathogenic mycobacteria. Interestingly, despite sequence homology and apparent redundancy, PE_PGRS proteins seem to have evolved a peculiar function. In this review, we summarize the actual knowledge on this elusive protein family in terms of evolution, structure, and function, focusing on the role of PE_PGRS in TB pathogenesis. We provide an original hypothesis on the role of the PE domain and propose a structural model for the polymorphic PGRS domain that might explain how so similar proteins can have different physiological functions.</p
Imino Acids and Collagen Triple Helix Stability:  Characterization of Collagen-like Polypeptides Containing Hyp-Hyp-Gly Sequence Repeats
The analysis of factors contributing to the stability of proteins is a subject of intense debate. Particularly challenging is the study of structural proteins, since their function is their structure. Among these is collagen, the key structural component of bones, skin, cartilage, tendons, and other connecting tissues. It is well established that the collagen triple helix is characterized by the presence of hydroxyproline, whose content modulates triple helix thermal stability according to the requirement of the host organism. Because of the complexity and the fibrous nature of collagen, data on the stability and structure of this protein have been mainly obtained by the use of collagen-like polypeptides. On the basis of CD characterization of collagen-like polypeptides we here show that the presence of Hyp at the X position of repeating triplets Hyp-Hyp-Gly stabilizes the triple helix significantly. This extra-stabilization has been ascribed, by using molecular modeling, to the formation of a hydrogen bond between Hyp residues belonging to the X and the Y positions of adjacent chains. This communication also provides a comprehensive interpretation of the ensemble of available data on polypeptides containing proline derivatives
Structural and dynamic features of PASTA domains with different functional roles
Structural and dynamic features of PASTA domains with different functional role
A Loose Domain Swapping Organization Confers a Remarkable Stability to the Dimeric Structure of the Arginine Binding Protein from <i>Thermotoga maritima</i>
<div><p>The arginine binding protein from <i>Thermatoga maritima</i> (TmArgBP), a substrate binding protein (SBP) involved in the ABC system of solute transport, presents a number of remarkable properties. These include an extraordinary stability to temperature and chemical denaturants and the tendency to form multimeric structures, an uncommon feature among SBPs involved in solute transport. Here we report a biophysical and structural characterization of the TmArgBP dimer. Our data indicate that the dimer of the protein is endowed with a remarkable stability since its full dissociation requires high temperature as well as SDS and urea at high concentrations. In order to elucidate the atomic level structural properties of this intriguing protein, we determined the crystallographic structures of the apo and the arginine-bound forms of TmArgBP using MAD and SAD methods, respectively. The comparison of the liganded and unliganded models demonstrates that TmArgBP tertiary structure undergoes a very large structural re-organization upon arginine binding. This transition follows the Venus Fly-trap mechanism, although the entity of the re-organization observed in TmArgBP is larger than that observed in homologous proteins. Intriguingly, TmArgBP dimerizes through the swapping of the C-terminal helix. This dimer is stabilized exclusively by the interactions established by the swapping helix. Therefore, the TmArgBP dimer combines a high level of stability and conformational freedom. The structure of the TmArgBP dimer represents an uncommon example of large tertiary structure variations amplified at quaternary structure level by domain swapping. Although the biological relevance of the dimer needs further assessments, molecular modelling suggests that the two TmArgBP subunits may simultaneously interact with two distinct ABC transporters. Moreover, the present protein structures provide some clues about the determinants of the extraordinary stability of the biomolecule. The availability of an accurate 3D model represents a powerful tool for the design of new TmArgBP suited for biotechnological applications.</p></div
(2Fo-Fc) electron density map contoured around the arginine ligand (2.0 σ). Arginine interacting residues are highlighted.
<p>(2Fo-Fc) electron density map contoured around the arginine ligand (2.0 σ). Arginine interacting residues are highlighted.</p
Refinement statistics.
<p>Values in parentheses are for higher resolution shells (2.53–2.49 Å and 1.52–1.47 Å for Holo and ApoTmArgBP, respectively).</p
Isothermal titration calorimetry experiments with (A) arginine and (B) glutamine.
<p>Top panels report raw data for the titrations at 25°C, whereas bottom panels report integrated heats of binding obtained from the raw data after subtracting the heats of dilution. The solid line (in A) represents the best curve fit to the experimental data using the ‘one set of sites’ model from MicroCal Origin.</p
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