04. april 2020
Glycoproteins are polypeptides decorated with oligosaccharides. They are prominent in eukaryotes and fulfill important biological roles e.g. cell signaling. Their biosynthesis occurs in the ER via the transfer of a carbohydrate precursor onto polypeptides. The precursor is obtained through a process catalyzed by glycosyltransferases. Recently, the detailed structure of yeast glucosyltransferase was reported. Here, I will discuss this structure as well as its current functional understanding.
06. maart 2020
Most proteins are exported linearly, while a subset is translocated folded. The bacterial Tat system is the best characterized system for the export of folded proteins. Although most mitochondria lack the Tat system, they retained a typical Tat-dependent substrate protein, RISP. In mitochondria, its export requires Bcs1 an AAA protein with the function of assembly factor. Recently, detailed structures of Bcs1 were reported. Here, I will discuss these as well as our functional understanding.
03. februari 2020
The threat of increasing antibiotic resistance emphasizes the need for novel drug targets. The inhibition of SPaseII, a key enzyme in the maturation of bacterial lipoproteins, by globomycin and myxovirescin shows that it is an effective drug target. The recent high-resolution structures of SPaseII complexed with these antibiotics revealed that they inhibit SPaseII by acting as a non-cleavable catalytic intermediate. Here, I will discuss these structures as well as their functional understanding.
30. december 2019
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.
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.

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