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Transcription Start Site Mapping Using Super-low Input Carrier-CAGE
Published on: June 26, 2019
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Slc11 Synapomorphy: A Conserved 3D Framework Articulating Carrier Conformation Switch.
1Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique (INRS), Laval, QC H7V 1B7, Canada.
International Journal of Molecular Sciences
|October 28, 2023
Summary
The Slc11 family of transmembrane carriers uses proton gradients to import essential metal ions like manganese and iron. Key evolutionary sites (synapomorphy) control metal selectivity and transport, even in rapidly evolving bacterial pathogens.
Area of Science:
- Biochemistry
- Molecular Biology
- Evolutionary Biology
Background:
- Transmembrane carriers of the Slc11 family are crucial for importing essential divalent metal ions (Me2+), such as manganese and iron, utilizing proton motive force.
- Conserved across prokaryotes (MntH) and eukaryotes (Nramp), Slc11 carriers exhibit high-affinity Me2+ import, with repeated evolution of proton-coupled transport mechanisms.
- Bacterial acquisition of Nramp genes suggests adaptive evolution benefiting opportunistic pathogens.
Purpose of the Study:
- To elucidate the evolutionary mechanisms and structural basis of Slc11 family transmembrane carriers.
- To investigate the role of specific evolutionary conserved sites (synapomorphy) in metal ion selectivity and transport.
- To compare carrier dynamics and plasticity between different bacterial clades (MCb and MCg) and their eukaryotic ancestors.
Main Methods:
- Utilized AlphaFold (AF2)/Colabfold (CF) for 3D structural predictions of bacterial Slc11 sequences.
- Employed in silico mutagenesis targeting putative synapomorphic sites and networked residue communities.
- Compared native and mutant structural models to analyze conformational changes (outwardly open to inwardly open states) and gate mechanisms.
Main Results:
- AF2/CF models revealed intermediates of the MCb clade transitioning between open and closed states, driven by synapomorphic sites.
- Slc11 synapomorphy was identified as a key determinant for Me2+-selective conformational switching, controlling inner and outer gates.
- MCg1 xenologs showed distinct structural plasticity and altered proton networks, yet synapomorphic sites also regulated their gate mechanisms, albeit with clade-specific epistatic interactions.
Conclusions:
- Slc11 synapomorphy forms a conserved 3D network essential for metal-selective conformational switching in transmembrane carriers.
- Divergent evolutionary pathways in clades like MCg1, particularly in genera such as *Bordetella* and *Achromobacter*, impact carrier shape and dynamics through epistatic interactions.
- The core mechanism of Me2+-selective transport is maintained across evolving clades, adapting to diverse environmental pressures.
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