Morphological Change of Cell Membrane by Interaction with Domain‐Swapped Cytochrome c Oligomers

Abstract

Monomeric cyt c has been reported to bind to the mitochondrial membrane by electrostatic and hydrophobic interactions with anionic phospholipids. We have previously shown that domain-swapped oligomeric cyt c retains the secondary structure of the monomer, and its surface possesses a larger area and more charges compared to the monomer. However, the effect of oligomerization of cyt c on cells has yet to be revealed. Herein, we investigated the interaction of oligomeric cyt c with anionic phospholipid-containing vesicles and the outer membrane of HeLa cells. Oligomeric cyt c interacted more strongly than monomeric cyt c with anionic phospholipid-containing vesicles and the outer membrane of HeLa cells. Oligomeric cyt c induced lateral phase separation of lipids in LUVs and GUVs, thereby leading to membrane disruption, whereas monomeric cyt c did not. Morphological changes in HeLa cells resulted from interaction with oligomeric cyt c, but little from interaction with the monomer. These results show that domain-swapped oligomeric proteins might exhibit properties different to those of monomer in cell systems.

The crystal structure of heme d1 biosynthesis-associated small c-type cytochrome NirC reveals mixed oligomeric states in crystallo

“…The relevance of dimer formation in NirC and the associated different levels of asymmetry are not clear at present. Previous work with eukaryotic monoheme c-type cytochromes suggested that 3D-domainswapped oligomers are involved in apoptosis (Junedi et al, 2014), which seems to be in line with the finding that several other 3D-domain-swapped proteins have a regulatory function. Examples include bovine RNase, where only the dimer displayed toxicity towards tumour cells (Di Donato et al, 1995) or the regulatory domain of α-isopropylmalate synthase of Mycobacterium tuberculosis, which forms via 3D domain swapping (Koon et al, 2004).…”

Control of catalysis in globin coupled adenylate cyclase by a globin-B domain

“…Domain swapping as envisioned for HemAC-Lm is a comparatively common characteristic among heme proteins, like cytochrome c [28][29][30][31], myoglobin [32,33], NO synthase [34], nitrite reductase [35], hemophore HasA [36] and methyl accepting chemotaxis protein [37]. However, the swapped Mb dimeric structure displays a similar oxygen-binding properties as that of its monomer [32].…”

“…However, the swapped Mb dimeric structure displays a similar oxygen-binding properties as that of its monomer [32]. Recently, researchers have suggested that the domain-swapped structure of dimeric cyt c displays different characteristics from those of its monomer [29,31]. In general, domains from adjacent subunits interact with each other when oligomerization takes place in the evolution of the protein's structure.…”

Study on Unsteady Combustion Behaviors of AP/HTPB Base‐Bleed Propellants under Transient Depressurization Conditions

“…Recently, we found that intermolecular hydrophobic interactions in cyt c at the early stage of protein folding controls the formation of the oligomer by domain swapping 16. The domain‐swapped dimer of cyt c exhibited different properties from those of its monomer,14b,d although the domain‐swapped Mb dimer exhibited a similar oxygen‐binding character as that of its monomer 15. In this study, we show that domain swapping could be used to design a heterodimeric protein of Mb, and this method may be a new approach for creating artificial proteins.…”