The structural dynamics of full-length divisome transmembrane proteins FtsQ, FtsB, and FtsL in FtsQBL complex formation

Kong, Wai-Po; Gong, Furong; So, Pui‐Kin; Chen, Yu Wai; Chan, P.H.; Leung, Yun-Chung; Wong, Kwok Yin

doi:10.1016/j.jbc.2022.102235

Cited by 2 publications

(8 citation statements)

References 44 publications

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“…On forming the complex, the whole periplasmic domain of FtsQ is locked into one configuration by anchoring with FtsB and FtsL, and this hinge is no longer flexible. However, this dynamic change was not detected experimentally [29] . The flexibility of FtsQ residues 226–241 is lost on complexation because they are in the vicinity of the three strands (FtsQ β12, FtsB β1, and FtsL β1) at the trimeric interface.…”

Section: Resultssupporting

confidence: 92%

“…The RMSF of the FtsQ β-domain (residues 160–257) and that of the β3 to β5 hinge region (residues 124–139) decreased similarly by ∼0.5 Å, in the FtsQBL state compared to those in the free state. These increases in rigidity on complexation were not as significant as our previous study at the minute scale [29] . Noticeably, two regions in FtsQ have RMSF reduced by> 1 Å on complexation, namely, residues 79–92 (loop between α1 and α2) and 226–241 (C-terminal half of α5 and its trailing loop).…”

Section: Resultsmentioning

confidence: 92%

“…There have been several experimental attempts to derive structural information about the FtsQBL complex, including our use of hydrogen/deuterium exchange mass spectrometry (HDX-MS) to study the detergent-solubilized full-length complex of E. coli [29] . Until very recently, most of these studies were confined to the periplasmic soluble domains and their artificial fusion derivatives.…”

Section: Introductionmentioning

confidence: 99%

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The structural integrity of the membrane-embedded bacterial division complex FtsQBL studied with molecular dynamics simulations

Chen¹,

Kong²,

Wong³

2023

Computational and Structural Biotechnology Journal

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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The structural integrity of the membrane-embedded bacterial division complex FtsQBL studied with molecular dynamics simulations

Chen¹,

Kong²,

Wong³

2023

Computational and Structural Biotechnology Journal

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“…The additional interactions seen in the model involve the loop between two sheets of FtsQ (residues 194-197) and one face of the helical region of FtsB (residues 48, 52, 56 and 59). These may be due to the orientation of the proteins and not particularly responsible for binding, as deuterium uptake differences cannot confirm these interactions ( Kong et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…These interactions could result from FtsB binding to FtsQ with antiparallel β-sheet packing. Although this extension of the β-sheet stacking seems an elegant utilisation of the extended C-terminus region of FtsL which is otherwise disordered, deuterium uptake studies do not provide sufficient validation for this aspect of the model ( Kong et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

Mapping the FtsQBL divisome components in bacterial NTD pathogens as potential drug targets

Kaur

Lynn

2023

Front. Genet.

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Cytokinesis is an essential process in bacterial cell division, and it involves more than 25 essential/non-essential cell division proteins that form a protein complex known as a divisome. Central to the divisome are the proteins FtsB and FtsL binding to FtsQ to form a complex FtsQBL, which helps link the early proteins with late proteins. The FtsQBL complex is highly conserved as a component across bacteria. Pathogens like Vibrio cholerae, Mycobacterium ulcerans, Mycobacterium leprae, and Chlamydia trachomatis are the causative agents of the bacterial Neglected Tropical Diseases Cholera, Buruli ulcer, Leprosy, and Trachoma, respectively, some of which seemingly lack known homologs for some of the FtsQBL complex proteins. In the absence of experimental characterization, either due to insufficient resources or the massive increase in novel sequences generated from genomics, functional annotation is traditionally inferred by sequence similarity to a known homolog. With the advent of accurate protein structure prediction methods, features both at the fold level and at the protein interaction level can be used to identify orthologs that cannot be unambiguously identified using sequence similarity methods. Using the FtsQBL complex proteins as a case study, we report potential remote homologs using Profile Hidden Markov models and structures predicted using AlphaFold. Predicted ortholog structures show conformational similarity with corresponding E. coli proteins irrespective of their level of sequence similarity. Alphafold multimer was used to characterize remote homologs as FtsB or FtsL, when they were not sufficiently distinguishable at both the sequence or structure level, as their interactions with FtsQ and FtsW play a crucial role in their function. The structures were then analyzed to identify functionally critical regions of the proteins consistent with their homologs and delineate regions potentially useful for inhibitor discovery.

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The structural dynamics of full-length divisome transmembrane proteins FtsQ, FtsB, and FtsL in FtsQBL complex formation

Cited by 2 publications

References 44 publications

The structural integrity of the membrane-embedded bacterial division complex FtsQBL studied with molecular dynamics simulations

The structural integrity of the membrane-embedded bacterial division complex FtsQBL studied with molecular dynamics simulations

Mapping the FtsQBL divisome components in bacterial NTD pathogens as potential drug targets

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