21. Mar. 2024

Cells and their components, such as mitochondria, are surrounded by semi-permeable membranes. These biological barriers are made up mainly of phospholipids and embedded proteins. Membranes separate the cell and its components from the surrounding space and allow only selected molecules to pass through. Scientists at CEITEC have now found that proteins that allow other proteins to burrow into the membrane could facilitate the transport of phospholipids across the membrane in the same way.

Biological membranes are mainly made up of phospholipids and proteins. While phospholipids are responsible for the basic properties of membranes, proteins typically provide transport and metabolic functions. However, many membrane proteins do not enter the membrane easily, so there are other membrane proteins, called insertases, that help proteins to insert into the membrane. One of these insertases is the mitochondrial protein MTCH2. Biophysicists Robert Vácha and Ladislav Bartoš from CEITEC Masaryk University have now discovered that this protein has also another function. It also helps to pass through the membrane a second important type of membrane molecule, phospholipids, and thus acts as a scramblase, a type of protein that facilitates the movement of phospholipids between the inner and outer layers of the lipid bilayer in the cell membrane. This movement is crucial for the proper composition and functioning of cell membranes. The team, which includes the authors of the current study published in the journal Structure, previously identified the first ever mitochondrial scramblase, the VDAC protein. Now, MTCH2 joins this group of proteins.

"Simulations have allowed us to reveal that phospholipid transport takes place on the surface of MTCH2 along a path for the insertion of proteins," describes Robert Vácha. "Proteins are made up of building blocks known as amino acids. These have different properties depending on their chemical composition. On the surface of the MTCH2 protein there is a long groove with amino acids that do not like the membrane environment and therefore locally disrupt and thin the membrane. This disruption of the membrane then allows other proteins to insert into the membrane and phospholipids to pass through it," explains Ladislav Bartoš.

The discovery that both membrane-embedding proteins and phospholipid transport can be facilitated in an identical way is important for understanding the principles of transport across cell membranes. "It is likely that other insertases or proteins with similar functions act simultaneously as scramblases," speculates Robert Vácha. Understanding cell membranes and the transport of molecules across them is crucial for drug development and technological applications.

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