Defective membrane proteins are the cause of diseases such as cystic fibrosis. This is a heritable disease caused by mutations in the CFTR gene that encodes a chloride channel. Current CF therapies rescue CFTR’s channel function and are based on small molecule drugs (correctors) that target the defects caused by CF mutations. Structures of human CFTR bound to correctors were reported recently. Here, I will discuss these structures as well as their functional understanding.
Metal ions are essential for life because these are used as enzymatic cofactors in metabolic processes. In bacteria, metal ion uptake is catalyzed by ABC transporters, a conserved class of membrane-embedded proteins. However, it is unclear how metal ions are imported. Recently, the structure of a bacterial ABC manganese importer was reported. Here, I will discuss its structural features as well as the mechanistic bases of metal ion specificity and import.
Heme is an established protein cofactor that used in a variety of biological processes. Heme b and c are commonly found in proteins. Proteins that contain heme c are known as cytochromes c and function as electron carriers. In bacteria, cytochrome c assembly is performed by eight membrane-embedded proteins (CcmABCDEFGH). Recently, the atomic structure of bacterial CcmF was determined. Here, I will discuss this structure as well as its functional understanding.
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.
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.
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.
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.
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.
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.
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.