16. november 2019
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.
15. oktober 2019
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.
04. september 2019
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.
12. juli 2019
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.
11. juni 2019
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.
12. mei 2019
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.
09. april 2019
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.
12. maart 2019
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.
14. februari 2019
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
16. januari 2019
The Sec complex is key for protein export. In eukaryotes, Sec61 facilitates protein transport across the ER membrane. This can occur post or co-translationally and requires a different Sec61 system. In yeast, post-translational export is performed by the Sec61 pore and the Sec62/Sec63 complex. Recent structures of the post-translational Sec complex have provided crucial insight into this. Here, I will discuss these novel structures and our understanding of post-translational translocation.

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