1pc3
Crystal structure of the extracellular phosphate ABC transport receptor (PstS-1) and immunodominant antigen of M. tuberculosis.Crystal structure of the extracellular phosphate ABC transport receptor (PstS-1) and immunodominant antigen of M. tuberculosis.
Structural highlights
FunctionPSTS1_MYCTU Functions in inorganic phosphate uptake, although probably not the main uptake protein under phosphate starvation (PubMed:15731097, PubMed:20933472). Binds phosphate; probably able to bind both H(2)PO(4)(-) and HPO(4)(2-) (PubMed:8294447, PubMed:12842040). Part of the ABC transporter complex PstSACB involved in phosphate import (Probable).[1] [2] [3] [4] A host TLR2 agonist (toll-like receptor), shown experimentally for human and mouse (PubMed:1906192, PubMed:19362712). Requires both host TLR1 and TLR2 as coreceptors to elicit host response in mouse (TLR6 may also play a role) neither CD14 or CD36 function as accessory receptors (PubMed:19362712). Protein purified from culture filtrate induces host (human) monocytes to produce TNF-alpha, IL-6 and IL-12 p40 (IL12B) via ERK1/2 (MAPK3 and MAPK1) and p38 MAPK pathways; MEK inhibitors U0126 and PD98059 and p38 inhibitor SB203580 block most cytokine production (PubMed:16622205). Host ERK1/2 and p38 MAPK activation is mediated mainly by TLR2, but also partially by TLR4, and unlike the case for lipoprotein LpqH the protein moiety of PstS1 seems to be the antigenic agent (PubMed:16622205). Greater activation of ERK1/2 and p38 MAPK is seen in patients with active pulmonary tuberculosis than in tuberculin-negative patients (PubMed:16622205). Induces apoptosis when incubated with human monocyte-derived macrophages via TLR2 (PubMed:19140873). Protein purified from culture filtrate acts via TLR2 and TLR4 to induce host macrophage (shown for mouse) endoplasmic reticulum stress-mediated apoptosis via MAPK (at least JNK), C-C motif chemokine 2 (MCP-1, Ccl2) and ZC3H12 endoribonucleases (MCPIP, Zc3h12) (PubMed:25544271). Functions as an adhesin, binds to human and mouse macrophages via mannose residues, binds to the mouse macrophage mannose receptor (possibly Mrc1) and mediates bacterial phagocytosis (PubMed:25359607).[5] [6] [7] [8] [9] [10] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 2.16 A structure of the phosphate-bound PstS-1, the primary extracellular receptor for the ABC phosphate transporter and immunodominant species-specific antigen of Mycobacterium tuberculosis, has been determined. The phosphate, completely engulfed in the cleft between two domains, is bound by 13 hydrogen bonds, 11 of which are formed with NH and OH dipolar donor groups. The further presence of two acidic residues, which serve as acceptors of the protonated phosphate, is key to conferring stringent specificity. The ion-dipole interactions between the phosphate and dipolar groups compensate the ligand's isolated negative charges. Moreover, the surprise finding that the electrostatic surface in and around the cleft is intensely negative demonstrates the power of ion-dipole interactions in anion binding and electrostatic balance. Additional functional features include both the flexible N-terminal segment that tethers PstS-1 on the cell surface and the hinge between the two domains, which should facilitate snaring the phosphate in the medium. Crystal structure of M tuberculosis ABC phosphate transport receptor: specificity and charge compensation dominated by ion-dipole interactions.,Vyas NK, Vyas MN, Quiocho FA Structure. 2003 Jul;11(7):765-74. PMID:12842040[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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