ATP binding and hydrolysis disrupt the high-affinity interaction between the heme ABC transporter HmuUV and its cognate substrate-binding protein

Qasem-Abdullah, Hiba; Perach, Michal; Livnat-Levanon, Nurit; Lewinson, Oded

doi:10.1074/jbc.m117.779975

Cited by 17 publications

(17 citation statements)

References 60 publications

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“…With respect to the mechanism of the heme transport by BhuUV-T, our mechanism proposed for BhuUV-T is apparently similar to that for the molybdate importer MolBC, but somewhat different from those for BtuCD-F and HmuUV. 11,37,63–66 For example, the closure of the cytoplasmic gate II in the proposed IF-to-OF transition pathway of BhuUV-T is consistent with an electron paramagnetic resonance (EPR) spectroscopy study on MolBC. 63 Moreover, key features in the crystal structure of MolBC are consistent with those of BhuUV.…”

Section: Discussionsupporting

confidence: 79%

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Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

Tamura

Sugimoto

Shiro

et al. 2018

Preprint

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28 29 ATP-binding cassette (ABC) transporters are integral membrane proteins that 30 translocate a wide range of substrates across biological membranes, harnessing free 31 energy from the binding and hydrolysis of ATP. To understand the mechanism of the 32 inward-to outward-facing transition that could be achieved by tight regulation of 33 ATPase activity through extensive conformational changes of the protein, we applied 34 template-based iterative all-atom molecular dynamics (MD) simulation to the heme 35 ABC transporter BhuUV-T. The simulations, together with biased MDs, predict two 36 new conformations of the protein, namely, occluded (Occ) and outward-facing (OF) 37 conformations. The comparison between the inward-facing crystal structure and the 38 predicted two structures shows atomic details of the gating motions at the 39 transmembrane helices and dimerization of the nucleotide-binding domains (NBDs). 40 The MD simulations further reveal a novel role of the ABC signature motifs 41 (LSGG[Q/E]) at the NBDs in decelerating ATPase activity in the Occ form through 42 sporadic flipping of the side chains of the LSGG[Q/E] catalytic serine residues. The 43 orientational changes are coupled to loose NBD dimerization in the Occ state, whereas 44 they are blocked in the OF form where the NBDs are tightly dimerized. The 45 chemo-mechanical coupling mechanism may apply to other types of ABC transporters 46 having the conserved LSGG[Q/E] signature motifs. 47Occ state and closure of the cytoplasmic gate are thought to result from the binding of 129 ATP and dimerization of the NBDs (BhuVs) (Figure 1c). The question which then arises 130 is: how is the hydrolysis of ATP prevented in the Occ state, such that futile cycling back 131 to the IF state is avoided, before formation of the OF state? To solve this problem, we 132 analyzed MD trajectories of BhuUV-T starting from predicted Occ and OF 133 conformations and arrived at a novel chemo-mechanical coupling mechanism that 134 regulates ATPase activity by way of reorientation of the serine residues of the 135 LSGG[Q/E] motifs in type II ABC transporters. The proposed mechanism likely 136

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Section: Discussionsupporting

confidence: 79%

“…11,37 These studies imply some mechanistic divergence among the type II ABC importer family, a view supported by a recent biochemical study on HmuUV. 66…”

Section: Discussionmentioning

confidence: 99%

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

Tamura

Sugimoto

Shiro

et al. 2018

Preprint

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“…Transport of heme across the inner membrane is energy dependent and is often facilitated by an ATP-binding cassette (ABC) transporter and a periplasmic binding protein (PBP) (Qasem-Abdullah et al, 2017). The PBP is responsible for transporting the heme between the two membranes and to the ABC transporter.…”

Section: Introductionmentioning

confidence: 99%

Heme Uptake and Utilization by Gram-Negative Bacterial Pathogens

Richard

Kelley

Johnson

2019

Front. Cell. Infect. Microbiol.

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Iron is a transition metal utilized by nearly all forms of life for essential cellular processes, such as DNA synthesis and cellular respiration. During infection by bacterial pathogens, the host utilizes various strategies to sequester iron in a process termed, nutritional immunity. To circumvent these defenses, Gram-negative pathogens have evolved numerous mechanisms to obtain iron from heme. In this review we outline the systems that exist in several Gram-negative pathogens that are associated with heme transport and utilization, beginning with hemolysis and concluding with heme degradation. In addition, Gram-negative pathogens must also closely regulate the intracellular concentrations of iron and heme, since high levels of iron can lead to the generation of toxic reactive oxygen species. As such, we also provide several examples of regulatory pathways that control heme utilization, showing that co-regulation with other cellular processes is complex and often not completely understood.

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“…ATP binds with the NBD domain and provides energy by ATP, and the TMDs domains provide a path for the cargo to go through the cell membrane. Additionally, ABC transporter needs a SBP, substrate-binding protein, to carry the substrate outside the membrane reaching to the TMD domain of ABC transporters [51]. solution [56].…”

Section: The Response Of Strain St7 At Stationary Phase Under Mn(ii) mentioning

confidence: 99%

Mechanism of manganese oxidization of Bacillus safensis strain ST7 isolated from the soil of mineral area

X¹,

Hong²,

Tian³

et al. 2020

Preprint

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Background: The manganese pollution is very serious surrounding the mine area, which could be enriched and harmful to animal, plant and human. Manganese oxidation bacteria (MOB) can completely remove the toxicity of Mn(II) with diverse mechanisms. Results: To seek a resource and disclose the oxidation mechanism of MOB, we isolated the Bacillus safensis strain ST7 from the soil of Songtao manganese mine in Guizhou province, China. Strain ST7 could survive in media containing 2200 mg/L Mn(II) with the Mn(II) removal efficiency of 82% after seven days cultivation. The rate was 7.75 μmol/L of Mn(II) each day detected by LBB method. The manganese oxides appeared after stationary growth phase and lots of irregular precipitates were observed on the surface of bacteria by scanning electron microscopy (SEM). We further constructed eight cDNA libraries at two growth stages of strain ST7, at which the first stage is the mid-exponential growth phase (stage1) and the second one at the onset of stationary phase (stage2). The gene expression patterns were analyzed across the entire transcriptome under 250 mg/L Mn(II) stress by using Illumina Hiseq platform. After mapping to the reference B. safensis genome, we detected 3574 expressed genes from the eight libraries. At the first stage, 1040 differently expressed genes (DEGs) were determined with 502 genes up-regulated in Mn(II) dealt group. For the second stage, 760 genes were increased and 702 genes down-regulated under Mn(II) stress. Of those, the expressed trend of seventeen random selective genes were confirmed by RT-qPCR method. Only nine high expressed DEGs were screened out and all of them were up-regulated in the manganese dealt group at stage1. The great changes at stage 1 were focused on the genes related with siderophore synthesis to help Mn(II) uptake and oxidation and gene cheA to elevate the chemotaxis and the motility of bacteria. It was observed that the motility of strain ST7 was much active in the media with Mn(II) supply. And the expression level of gene601, coded for a multicopper oxidase (MCO) enzyme-like protein, raised about 3.66 times than its control group at stage 1. By using homologous recombination technology, it was demonstrated that the Mn(II) oxidase ability decreased obviously when the gene601 of B. safensis strain ST7 was knocked out. For stage 2 of strain ST7 dealt with Mn(II), there were nineteen genes related with sporulation and most of flagellum genes were inhibited. However, lots of transporters genes were augmented to function as pumps to extrude manganese outside of the bacterium cell. Conclusions: In a brief, the isolated B. sanfensis took two strategies against Mn stress including manganese oxidation at exponential growth stage and transformation of Mn(II) at stationary phase. The strain could be used to treat the environmental manganese pollution to minimize the use of chemical oxidants as a cost-effective technology.

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ATP binding and hydrolysis disrupt the high-affinity interaction between the heme ABC transporter HmuUV and its cognate substrate-binding protein

Cited by 17 publications

References 60 publications

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

Heme Uptake and Utilization by Gram-Negative Bacterial Pathogens

Mechanism of manganese oxidization of Bacillus safensis strain ST7 isolated from the soil of mineral area

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