17. mei 2021
Long road to ruin
Secretory proteins initially transit the ER and are only allowed to leave after they have attained their native structure. Misfolded proteins are transported back from the ER into the cytosol and are degraded by the proteasome. This process is known as ERAD. Ubiquitin ligases play an essential role in all ERAD pathways. Recently, detailed structures of the yeast Hrd1 ubiquitin ligase complex were reported. Here, I will discuss these structures as well as their functional understanding.
25. februari 2021
Guardians of the proteome
Chaperones play an essential cellular role in the folding and refolding of proteins. In fact, chaperones are a key component of the cell’s quality control system that monitors the functional integrity of the proteome. The following chaperone families are known: Hsp40, Hsp60, Hsp70, Hsp90, Hsp100 and the small Hsps. Recently, detailed structures of the human Hsp60 chaperonin complex were reported. Here, I will discuss these structures as well as their current functional understanding.
16. december 2020
GPCRs represent the largest family of eukaryotic membrane proteins. In humans, GPCRs control almost every physiological aspect because they activate cellular signaling pathways upon stimulation by extracellular ligands. Recently detailed structures of the human serotonin receptor bound to hallucinogens were presented, providing detailed insight into GPCR activation as well as association with G proteins. Here I will discuss these structures and their current functional understanding.
15. oktober 2020
Bacterial swimming was already reported in 1676. Most bacteria contain flagella, which enables them to move around in liquid environments. A flagellum represents a nanomachine that consists of three main parts: basal body, hook and filament. The basal body serves as rotary motor and comprises a rotor complex which is surrounded by stator complexes. Recently, structures of bacterial stator complexes were presented. Here, I will discuss these structures as well as their functional understanding.
06. september 2020
Two structural folds anchor proteins into the membrane; the alpha helix and beta barrel. Alpha helical proteins are found in all membranes, while beta barrel proteins are restricted the OM of bacteria, chloroplasts and mitochondria. How these proteins are assembled into the OM is poorly understood, although the bacterial BAM complex is essential for this. A detailed structuresof the substrate-bound BAM complex was presented. Here, I will discuss this structure and its mechanistic significance.
03. juli 2020
About 20-30% of the human proteome comprises integral membrane proteins. These are essential for proper cell functioning and are cotranslationally synthesized at the ER through the Sec61 translocon. Moreover, the ER contains other insertion factors that mediate membrane protein insertion such as EMC. The structure of human EMC was presented recently, providing mechanistic insight of membrane protein insertion. Here, I will discuss this structure as well as its current functional understanding.
03. juni 2020
Resistance to chemotherapeutics is a pressing problem in cancer therapy. This is often caused by ABC transporters that remove drugs from the cell. The export of toxic compounds by these proteins is powered by ATP hydrolysis. ABCG2 is a human transporter known to confer multidrug resistance in many tumors. Recently, detailed structures of ABCG2 in the apo state and bound to anticancer drugs were determined. Here, I will discuss these structures as well as their current functional understanding.
07. mei 2020
Bacteria display a large variety in cell shape but rely on peptidoglycan to maintain their shape. This is a mesh-like biopolymer that surrounds the cytoplasmic membrane and is made up of long glycan strands cross-linked by short peptides. The enzymes that catalyze peptidoglycan biosynthesis are known as peptidoglycan synthases. Recently, the structure of a novel a peptidoglycan synthase was elucidated. Here, I will discuss this structure as well as its functional understanding.
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.

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