Bacterial respiratory chains offer greater metabolic flexibility than mitochondrial ones, while they are energetically less efficient. E. coli, contains a respiratory system that allows it to grow aerobically and anaerobically. Aerobic grown E. coli cells express two terminal oxidases, cytochrome bo-oxidase and bd-oxidase, that reduce oxygen to water. Recently, a detailed structure of E. coli bd-oxidase was reported. Here, I will discuss this structure and its current functional understanding.
Mitochondria are essential eukaryotic organelles. Their activity depends on the correct functioning of its proteome. This comprises about 1500 proteins that are mainly nuclear-encoded and imported into the organelle. Therefore, mitochondria are equipped with specialized protein translocation nanomachines in their membranes. Recently, a detailed structure of the TOM complex was reported. Here, I will discuss this structure as well as its functional understanding.
Gram-negative bacteria possess dedicated protein secretion systems- type I through type VI. The type III injectisome is a nanomachine that spans the bacterial cell envelope and serves as protein-conducting channel. It is used by pathogens to transport virulence proteins directly into the host cytoplasm. Recent detailed structures have provided profound atomic insight into injectisome assembly and mechanism. Here I will discuss these structures as well as its current functional understanding.
Protein export is a crucial biological process. This is typically performed by a conserved protein-conducting channel termed the SecY complex in bacteria and Sec61 complex in eukaryotes. In bacteria, the export of most proteins is powered by SecA. This is an ATPase that couples ATP hydrolysis to protein export. Recently a detailed structure of the substrate-engaged SecA-SecY complex was presented. Here, I will discuss this structure as well as the current understanding of SecA functioning.
Membrane proteins are biologically and medically relevant. In fact, some genetic human diseases are caused by their misassembly e.g. cystic fibrosis, a lethal hereditary disorder. CF is caused by mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR). This is a chloride-conducting transmembrane channel. Recently, structures of human CFTR in complex with small molecule drugs were reported. Here, I will discuss these structures and our current understanding of CFTR.
Mitochondrial proteases are crucial for maintaining mitochondrial activity. These include ClpP, which in humans, is a key factor in different tumors, thereby contributing to the role of mitochondria as mediators of oncogenesis. Potent anticancer drugs have been developed that exert activity through hyperactivating ClpP. Recently, detailed structures of human ClpP in complex with these hyperactivators were reported. Here, I will discuss these structures as well as how these hyperactivators work.
The ability to rapidly export drugs from the cell represents a powerful mechanism of bacteria to achieve high-level multidrug resistance. P aeruginosa contains numerous efflux pumps, explaining its exceptionally high dug resistance. Of these, the MexAB-OprM system represents the best characterized multidrug efflux pump. Recently, novel structures of the MexAB-OprM pump were presented. Here I will discuss these structures as well as its functional understanding.
Gram-negative bacteria are insensitive to antibiotics effective against Gram-positives. This is because their cell wall contains a protective LPS layer that is produced in the cytoplasm and transported to the cell surface. This depends on Lpt proteins that form a bridge spaning the cell envelope. Recently structures of the Lpt complex responsible for LPS extraction and transfer to the Lpt bridge were reported. Here, I will discuss these structures as well as the understanding of LPS transport.
Cholesterol is linked with cardiovascular diseases and should not be viewed as bad because life would not be possible without it. The biosynthesis of cholesterol requires different enzymes e.g. SQLE. This is a flavin-dependent monooxygenase that is pharmaceutical relevant. Recently, structures of human SQLE have been reported contributing to the design of novel drugs. Here, I will discuss these structures as well as our current mechanistic understanding of this enzyme.
Mitochondria are essential eukaryotic organelles. Their proper activity is crucial for health. The mitochondrial inner membrane houses important protein complexes. Maintaining the quality of the IM proteome is key for safeguarding mitochondrial funtioning. Two proteases, i-AAA and m-AAA, play an important role in this process. Recent structures of these proteases offered profound insight into their functioning. Here, I will discuss these structures and how these enzymes handle substrate proteins
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