3.A.28. The AAA-ATPase, Bcs1 (Bcs1) Family

The mitochondrial AAA-ATPase, Bcs1, mediates topogenesis of the Rieske protein, Rip1, a component of respiratory chains in bacteria, mitochondria, and chloroplasts (Wagener et al. 2011). The oligomeric AAA-ATPase, Bcs1, is involved in export of the folded Fe-S domain of Rip1 across the inner membrane and insertion of its transmembrane segment into an assembly intermediate of the cytochrome bc1 complex. Structural elements in Rip1 are required for recognition and export by as well as ATP-dependent lateral release from the AAA-ATPase. In bacteria and chloroplasts, Rip1 uses the Tat machinery for topogenesis; however, mitochondria have lost this machinery during evolution, and a member of the AAA-ATPase family has taken over its function (Wagener et al., 2011).  Mutations in Bcs1 lead to different properties of the protein and different disease-related symptoms (Wagener and Neupert 2012).  A conserved α-helix in Bcs1 is required for Respiratory Complex III maturation (Sawamura et al. 2014). Human BCS1 has been implicated in human mitochondrial disorders (e.g. Björnstad and Gracile syndromes) (Ostojić et al. 2014). The outer membrane AAA-ATPase of Arabidopsis thaliana, AtOM66, affects cell death and pathogen resistance (Zhang et al. 2014). 

Kater et al. 2020 presented the structure of Saccharomyces cerevisiae Bcs1, an AAA-ATPase of the inner mitochondrial membrane. Bcs1 facilitates the translocation of the Rieske protein, Rip1, which requires folding and incorporation of a 2Fe-2S cluster before translocation and subsequent integration into the bc1 complex (TC# 3.D.3). Bcs1 assembles into an exclusively heptameric homo-oligomer, with each protomer consisting of an amphipathic transmembrane helix, a middle domain and an ATPase domain. Together they form two aqueous vestibules, the first being accessible from the mitochondrial matrix and the second positioned in the inner membrane, with both separated by the seal-forming middle domain. On the basis of this unique architecture, Kater et al. 2020 proposed an airlock-like translocation mechanism for folded Rip1.



This family belongs to the AAA-ATPase Superfamily.

 

References:

Kater, L., N. Wagener, O. Berninghausen, T. Becker, W. Neupert, and R. Beckmann. (2020). Structure of the Bcs1 AAA-ATPase suggests an airlock-like translocation mechanism for folded proteins. Nat Struct Mol Biol 27: 142-149.

Ostojić, J., J.P. Rago, and G. Dujardin. (2014). A novel mechanism involved in the coupling of mitochondrial biogenesis to oxidative phosphorylation. Microb Cell 1: 43-44.

Sawamura, R., T. Ogura, and M. Esaki. (2014). A conserved α helix of Bcs1, a mitochondrial AAA chaperone, is required for the Respiratory Complex III maturation. Biochem. Biophys. Res. Commun. 443: 997-1002.

Tamai, S., H. Iida, S. Yokota, T. Sayano, S. Kiguchiya, N. Ishihara, J. Hayashi, K. Mihara, and T. Oka. (2008). Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L. J Cell Sci 121: 2588-2600.

Wagener, N. and W. Neupert. (2012). Bcs1, a AAA protein of the mitochondria with a role in the biogenesis of the respiratory chain. J Struct Biol 179: 121-125.

Wagener, N., M. Ackermann, S. Funes, and W. Neupert. (2011). A pathway of protein translocation in mitochondria mediated by the AAA-ATPase Bcs1. Mol. Cell 44: 191-202.

Zhang, B., O. Van Aken, L. Thatcher, I. De Clercq, O. Duncan, S.R. Law, M.W. Murcha, M. van der Merwe, H.S. Seifi, C. Carrie, C. Cazzonelli, J. Radomiljac, M. Höfte, K.B. Singh, F. Van Breusegem, and J. Whelan. (2014). The mitochondrial outer membrane AAA ATPase AtOM66 affects cell death and pathogen resistance in Arabidopsis thaliana. Plant J. 80: 709-727.

Examples:

TC#NameOrganismal TypeExample
3.A.28.1.1

The mitochondrial chaperone (Wagener et al., 2011). Some proteins require completion of folding before translocation across a membrane into another cellular compartment, but the permeability barrier of the membrane should not be compromised. Kater et al. 2020 presented the structure of Saccharomyces cerevisiae Bcs1, an AAA-ATPase of the inner mitochondrial membrane. Bcs1 facilitates the translocation of the Rieske protein, Rip1, which requires folding and incorporation of a 2Fe-2S cluster before translocation and subsequent integration into the bc1 complex (TC# 3.D.3). Bcs1 assembles into an exclusively heptameric homo-oligomer, with each protomer consisting of an amphipathic transmembrane helix, a middle domain and an ATPase domain. Together they form two aqueous vestibules, the first being accessible from the mitochondrial matrix and the second positioned in the inner membrane, with both separated by the seal-forming middle domain. On the basis of this unique architecture, Kater et al. 2020 proposed an airlock-like translocation mechanism for folded Rip1.

Fungi

Bcs1 of Saccharomyces cerevisiae (P32839)

 
3.A.28.1.2

The mycorrhiza-induced mitochondrial AAA-ATPase, Bsc1

Fungi

Bsc1 of Laccaria bicolor (B0DYA3)

 
3.A.28.1.3

AAA-ATPase of 514 aas and one or two N-terminal TMSs, AATP1 or ASD. 

ATPase, ASD, of Arabidopsis thaliana

 
3.A.28.1.4

AAA-ATPase of 475 aas and 1 or 2 N-terminal TMSs.

ATPase of Arabidopsis thaliana (Mouse-ear cress)

 
3.A.28.1.5

AAA-ATPase, Bcs1 or Bcs1L of 419 aas and 2 or 3 TMSs. Bcs1 is a chaperone necessary for the assembly of mitochondrial respiratory chain complex III. It plays an important role in the maintenance of mitochondrial tubular networks, respiratory chain assembly and formation of the LETM1 complex 1 (Tamai et al. 2008).


Bcs1 of Homo sapiens