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The peptidase-containing ATP-binding cassette transporters (PCATs) are unique members of the ABC transporter family that proteolytically process and export peptides and proteins. Each PCAT contains two peptidase domains that cleave off the secretion signal, two transmembrane domains forming a translocation pathway, and two nucleotide-binding domains that hydrolyze ATP. Previously the crystal structures of a PCAT from (PCAT1) were determined in the absence and presence of ATP, revealing how ATP binding regulates the protease activity and access to the translocation pathway. However, how the substrate CtA, a 90-residue polypeptide, is recognized by PCAT1 remained elusive. To address this question, we determined the structure of the PCAT1-CtA complex by electron cryo-microscopy (cryo-EM) to 3.4 Å resolution. The structure shows that two CtAs are bound via their N-terminal leader peptides, but only one is positioned for cleavage and translocation. Based on these results, we propose a model of how substrate cleavage, ATP hydrolysis, and substrate translocation are coordinated in a transport cycle.
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() is the causative agent of tuberculosis (TB) and has evolved an incredible ability to survive latently within the human host for decades. The pathogen encodes for a low number of ATP-binding casset...
Typhoid toxin is a virulence factor for the bacterial pathogen Typhi, which causes typhoid fever in humans. After its synthesis by intracellular bacteria, typhoid toxin is secreted into the lumen of ...
Type VII secretion systems (T7SSs) are found in many disease related bacteria including Mycobacterium tuberculosis (Mtb). ESX-1 [early secreted antigen 6 kilodaltons (ESAT-6) system 1] is one of the f...
To understand the pathways involved in drug clearance from the body, quantitative evaluations of the hepatobiliary transport of drugs are important. The organic anion transporting polypeptide (OATP) f...
Glucose-dependent insulinotropic polypeptide(GIP) has been suggested to stimulate the secretion of pancreatic polypeptide(PP), an islet hormone thought to regulate gut motility, appetite and glycem...
Drug-drug Interaction Study Using Rosuvastatin as a Breast Cancer Resistant Protein (Efflux Transporter), Organic Anion-transporting Polypeptide (OATP)1B1, and OATP1B3 (Uptake Transporters) Probe Substrate
Evaluation of the potential perpetrator effect of BAY1841788 (ODM-201) on rosuvastatin pharmacokinetics
Glucagon is a 29-amino acid peptide hormone of essential importance for glucose homeostasis. Hitherto glucagon has been believed to be secreted only from the pancreas, but recent studies s...
The investigators want to observe whether different doses of pancreatic polypeptide infusions influence gastric accommodation (measured as intragastric pressure changes during a liquid mea...
study hypothesis: treatment with GLP-1 and/or GIP is able to potentiate the maximal stimulated insulin secretion even in c-peptide negative type-1 diabetic patients classified as having no...
The effect of organic anion transporting polypeptide 1B1 (OATP1B1) transporter inhibition at clinical doses of fluvastatin, a biopharmaceutics drug disposition classification system (BDDCS...
A 36-amino acid pancreatic hormone that is secreted mainly by endocrine cells found at the periphery of the ISLETS OF LANGERHANS and adjacent to cells containing SOMATOSTATIN and GLUCAGON. Pancreatic polypeptide (PP), when administered peripherally, can suppress gastric secretion, gastric emptying, pancreatic enzyme secretion, and appetite. A lack of pancreatic polypeptide (PP) has been associated with OBESITY in rats and mice.
A subunit of the anaphase-promoting complex whose primary function is to provide structural support for the catalytic and substrate-recognition modules of the complex. Apc4, along with Apc5, tethers the tetratricopeptide-coactivator binding subcomplex to the main structural subunit, Apc1.
A subunit of the anaphase-promoting complex whose primary function is to provide structural support for the catalytic and substrate-recognition modules of the complex. Apc5, along with Apc4, tethers the tetratricopeptide-coactivator binding subcomplex to the main structural subunit, Apc1.
An 86-amino acid polypeptide, found in central and peripheral tissues, that displaces diazepam from the benzodiazepine recognition site on the gamma-aminobutyric acid receptor (RECEPTORS, GABA). It also binds medium- and long-chain acyl-CoA esters and serves as an acyl-CoA transporter. This peptide regulates lipid metabolism.
A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.