3.D.14. The HQNO-bound Alternative Complex III (HAC3) Family
The cryo-EM structure of HQNO-bound alternative complex III from the anoxygenic phototrophic bacterium Chloroflexus aurantiacus has been solved (Xin et al. 2024). All constituents known a dissimilar from those of Complex III from eikaryotes and proteobacteria, and consequently a novel family is assigned. Alternative complex III (ACIII) couples quinol oxidation and electron acceptor reduction with potential transmembrane proton translocation. It is compositionally and structurally different from the cytochrome bc1/b6f complexes but functionally replaces these enzymes in the photosynthetic and/or respiratory electron transport chains (ETCs) of many bacteria. However, the true compositions and architectures of ACIIIs have remained unclear, as do their structural and functional relevance in mediating the ETCs. Xin et al. 2024 determined cryogenic electron microscopy structures of photosynthetic ACIII isolated from Chloroflexus aurantiacus (CaACIIIp), in apo-form and in complexed form bound to a menadiol analog 2-heptyl-4-hydroxyquinoline-N-oxide. Besides 6 canonical subunits (ActABCDEF), the structures revealed conformations of 2 previously unresolved subunits, ActG and I, which contributed to the complex stability. The authors also elucidated the structural basis of menaquinol oxidation and subsequent electron transfer along the [3Fe-4S]-6 hemes wire to its periplasmic electron acceptors, using electron paramagnetic resonance, spectroelectrochemistry, enzymatic analyses, and molecular dynamics simulations. A unique insertion loop in ActE was shown to function in determining the binding specificity of CaACIIIp for downstream electron acceptors. This study broadens our understanding of the structural diversity and molecular evolution of ACIIIs, enabling further investigation of the (mena)quinol oxidoreductases-evolved coupling mechanism in bacterial energy conservation.
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This entry describes the HQNO-bound alternative complex III from the anoxygenic phototrophic bacterium Chloroflexus aurantiacus for which the structure has been determined at 1.9 Å resolution (Xin et al. 2024). A more detailed description is presented in the family description and especially by this reference. There are seven known subunites as follows: Subunits B, C, D, E, F, G, and I. They are to be found in NCBI under the general ID # 8X2J_ followed by the number of the subunit as indicated above. These subunits are:
B: 1029 aas and possibly 2 TMSs, 8X2J_B; FeS cluster-containing hydrogenase component-like protein
C: 486 aas and probably 10 TMSs, 8X2J_C: Polysulfide reductase, NrfD
D: 179 aas and 2 TMSs.
E: 205 aas and 1 N-terminal TMS
F: 411 aas and 10 TMSs. Subunits C and F are homologous, both with 10 TMSs, although they are distant in sequence.
G: 112 aas and 1 TMS
I: 37 aas and 1 TMS.
The 7 protein complex of the alternative complex III of Chloroflexus aurantiacus