Membrane Tethering of SepF, a Membrane Anchor for the Mycobacterium tuberculosis Z-ring

Dey, Souvik; Zhou, Huan‐Xiang

doi:10.1016/j.jmb.2022.167817

Cited by 15 publications

(18 citation statements)

References 26 publications

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“…Thus, whereas FtsQ participates in the E. coli divisome approximately midway through its development 22 , the Mtb homolog mediates the initial development of the Z-ring at the start of the cell division process. Another protein, SepF, has also been characterized as a membrane anchor of the Z-ring in B. subtilis, C. glutamicum, and Mtb 11, [14][15][16] . SepF is a water-soluble protein but tethers to membranes by an amphipathic helix at its N-terminus and, in the Mtb version, also Arg-rich stretches in the disordered linker preceding the FtsZ-binding core domain 16 .…”

Section: Discussionmentioning

confidence: 99%

“…Because the Z-ring is formed by the polymerization of the GTPase domain, direct binding of the FtsQ Arg/Ala-rich helix keeps the Z-ring in close proximity to the inner membrane. SepF has also been characterized as a membrane anchor of the Z-ring in B. subtilis , C. glutamicum , and Mtb ( 11, 14, 15, 19 ). It is a water-soluble protein but tethers to the membrane by an amphipathic helix at its N-terminus and, in the Mtb version, also by Arg-rich stretches in the disordered linker preceding the FtsZ-binding core domain ( 19 ).…”

Section: Figurementioning

confidence: 99%

“…SepF has also been characterized as a membrane anchor of the Z-ring in B. subtilis , C. glutamicum , and Mtb ( 11, 14, 15, 19 ). It is a water-soluble protein but tethers to the membrane by an amphipathic helix at its N-terminus and, in the Mtb version, also by Arg-rich stretches in the disordered linker preceding the FtsZ-binding core domain ( 19 ). The additional membrane interactions by the Mtb SepF linker brings the Z-ring into close proximity of the membrane.…”

Section: Figurementioning

confidence: 99%

“…However, Mtb has SepF 14 but no FtsA, and may have another unidentified membrane anchor of the Z-ring for redundancy. SepF has been studied as a membrane anchor of the Z-ring in Corynebacterium glutamicum 15 and Mtb 16 .…”

mentioning

confidence: 99%

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An Arg/Ala-Rich Helix in the N-Terminal Region ofM. tuberculosisFtsQ Anchors FtsZ to Membranes

Escobar

Dey

Smrt

et al. 2022

Preprint

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Mycobacteria tuberculosis (Mtb) inflicts a quarter of the worldwide population. Most drugs for treating tuberculosis target cell growth and division. With rising drug resistance, it becomes ever more urgent to better understand Mtb cell division. This process begins with the formation of the Z-ring via polymerization of FtsZ and anchoring of the Z-ring to the inner membrane. Here we show that the transmembrane protein FtsQ is a membrane anchor of the Mtb Z-ring. More specifically, FtsQ uses an Arg/Ala-rich helix in its otherwise disordered N-terminal cytoplasmic region to bind with the GTPase domain of FtsZ. Binding of FtsQ to the GTPase domain of FtsZ also has enormous implications for drug binding and Z-ring formation including its curvature.

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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

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An Arg/Ala-Rich Helix in the N-Terminal Region ofM. tuberculosisFtsQ Anchors FtsZ to Membranes

Escobar

Dey

Smrt

et al. 2022

Preprint

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“…13 Molecular dynamics (MD) simulations have much to offer in characterizing atomic details of IDP binding to membranes, as demonstrated in our recent studies. [22][23][24] Here we report MD simulation results of tau K19 bound to POPC/POPS membranes. Our MD simulations show that three amphipathic helices, one in each repeat, stably bind to the membrane.…”

mentioning

confidence: 99%

Partial Mimicry of the Microtubule Binding of Tau by Its Membrane Binding

MacAinsh

Zhou

2022

Preprint

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Tau, as typical of intrinsically disordered proteins (IDPs), binds to multiple targets including microtubules and acidic membranes. The latter two surfaces are both highly negatively charged, raising the prospect of mimicry in their binding by tau. The tau-microtubule complex was recently determined by cryo-EM. Here we used molecular dynamics simulations to characterize the dynamic binding of tau K19 to an acidic membrane. This IDP can be divided into three repeats, each containing an amphipathic helix. The three amphipathic helices, along with flanking residues, tether the protein to the membrane interface. The separation between and membrane positioning of the amphipathic helices in the simulations are validated by published EPR data. The membrane contact probabilities of individual residues in tau show both similarities to and distinctions from native contacts with microtubules. In particular, a Lys that is conserved among the repeats forms similar interactions with membranes and with microtubules, as does a conserved Val. This partial mimicry facilitates both the membrane anchoring of microtubules by tau and the transfer of tau from membranes to microtubules.

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Partial mimicry of the microtubule binding of tau by its membrane binding

MacAinsh

Zhou

2023

Protein Science

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Tau, as typical of intrinsically disordered proteins (IDPs), binds to multiple targets including microtubules and acidic membranes. The latter two surfaces are both highly negatively charged, raising the prospect of mimicry in their binding by tau. The tau‐microtubule complex was recently determined by cryo‐electron microscopy. Here, we used molecular dynamics simulations to characterize the dynamic binding of tau K19 to an acidic membrane. This IDP can be divided into three repeats, each containing an amphipathic helix. The three amphipathic helices, along with flanking residues, tether the protein to the membrane interface. The separation between and membrane positioning of the amphipathic helices in the simulations are validated by published EPR data. The membrane contact probabilities of individual residues in tau show both similarities to and distinctions from native contacts with microtubules. In particular, a Lys that is conserved among the repeats forms similar interactions with membranes and with microtubules, as does a conserved Val. This partial mimicry facilitates both the membrane anchoring of microtubules by tau and the transfer of tau from membranes to microtubules.

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Membrane Tethering of SepF, a Membrane Anchor for the Mycobacterium tuberculosis Z-ring

Cited by 15 publications

References 26 publications

An Arg/Ala-Rich Helix in the N-Terminal Region ofM. tuberculosisFtsQ Anchors FtsZ to Membranes

An Arg/Ala-Rich Helix in the N-Terminal Region ofM. tuberculosisFtsQ Anchors FtsZ to Membranes

Partial Mimicry of the Microtubule Binding of Tau by Its Membrane Binding

Partial mimicry of the microtubule binding of tau by its membrane binding

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