Role of Domain Swapping in the Hetero-Oligomeric Cytochrome b₆f Lipoprotein Complex

Abstract

Domain swapping that contributes to the stability of biologically crucial multisubunit complexes has been implicated in protein oligomerization. In the case of membrane protein assemblies, domain swapping of the iron–sulfur protein (ISP) subunit occurs in the hetero-oligomeric cytochrome b6f and bc1 complexes, which are organized as symmetric dimers that generate the transmembrane proton electrochemical gradient utilized for ATP synthesis. In these complexes, the ISP C-terminal predominantly β-sheet extrinsic domain containing the redox-active [2Fe-2S] cluster resides on the electrochemically positive side of each monomer in the dimeric complex. This domain is bound to the membrane sector of the complex through an N-terminal transmembrane α-helix that is “swapped’ to the other monomer of the complex where it spans the complex and the membrane. Detailed analysis of the function and structure of the b6f complex isolated from the cyanobacterium Fremyella diplosiphon SF33 shows that the domain-swapped ISP structure is necessary for function but is not necessarily essential for maintenance of the dimeric structure of the complex. On the basis of crystal structures of the cytochrome complex, the stability of the cytochrome dimer is attributed to specific intermonomer protein–protein and protein–lipid hydrophobic interactions. The geometry of the domain-swapped ISP structure is proposed to be a consequence of the requirement that the anchoring helix of the ISP not perturb the heme organization or quinone channel in the conserved core of each monomer.

Catalytic Reactions and Energy Conservation in the Cytochrome bc1 and b6f Complexes of Energy-Transducing Membranes

“…In view of the topographic arrangement of ISP, the functional module at the level of the Cyt bc 1 monomer consists of the Cyt b and Cyt c 1 and ISP linked to them through its ISP-HD, while also interacting with Cyt b and Cyt c 1 of the other monomer through its hydrophobic anchor. The same structure feature applies to Cyt b 6 f (see further) . The crystal structures of Cyt bc 1 revealed that large distances separate the cofactors from different monomers, except for the two hemes b L that are positioned close enough to allow electron transfer between the monomers (Figure ).…”

Oncogenic Mutations Differentially Affect Bax Monomer, Dimer, and Oligomeric Pore Formation in the Membrane

“…8 ). Of note, the mechanisms of mutant-controlled energy landscape shift that can either promote or impede the swapped dimer, are not limited to Bax, but observed for other proteins, including Grb7 62 , E-cadherin 63 , p38α 64 , LRRK2 65 , Protein L 66 , SPAK 67 and cytochrome complexes 68 . This suggests that the triggering or blocking swapped protein assemblies by mutations is a general phenomenon that plays an important role in human metabolism and broadly in the cell 69 , including in membrane pores as is the case here.…”

Structure‐based control of the rate limitation of photosynthetic electron transport

“…contains eight polypeptide subunits. The subunits containing redox co‐factors are: (a) the electron transport protein petA, the cyt f subunit, containing one trans‐membrane helix (TMH); (b) petB (cyt b 6 , 4 TMH); (c) petC, the Rieske 2Fe–2S protein, with a unique ‘domain‐swapped’ TMH ; and (d) petD or suIV (3 TMH), which corresponds to the C‐terminal half of the cyt b subunit of the cyt bc 1 complex in mitochondria or purple photosynthetic bacteria. The protein core in each monomer of the dimeric cyt complex contains five permanently bound metalloprotein redox prosthetic groups (four hemes, f , b p , b n ., and c n , and one 2Fe–2S cluster).…”