title: Cure and curse: E. coli heat-stable enterotoxin and its receptor guanylyl cyclase C.
abstract: Enterotoxigenic Escherichia coli (ETEC) associated diarrhea is responsible for roughly half a million deaths per year, the majority taking place in developing countries. The main agent responsible for these diseases is the bacterial heat-stable enterotoxin STa. STa is secreted by ETEC and after secretion binds to the intestinal receptor guanylyl cyclase C (GC-C), thus triggering a signaling cascade that eventually leads to the release of electrolytes and water in the intestine. Additionally, GC-C is a specific marker for colorectal carcinoma and STa is suggested to have an inhibitory effect on intestinal carcinogenesis. To understand the conformational events involved in ligand binding to GC-C and to devise therapeutic strategies to treat both diarrheal diseases and colorectal cancer, it is paramount to obtain structural information on the receptor ligand system. Here we summarize the currently available structural data and report on physiological consequences of STa binding to GC-C in intestinal epithelia and colorectal carcinoma cells.
authors: Lehrstuhl für Biopolymere und Forschungszentrum für Bio-Makromoleküle, Universität Bayreuth, Universitätsstraße, Bayreuth, Germany. philipp.weiglmeier@uni-bayreuth.de
authors: Philipp R
authors: PR
authors: Weiglmeier
authors: Paul
authors: P
authors: Rösch
authors: Hanna
authors: H
authors: Berkner
mesh_terms: D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003967:Diarrhea / Q000382:microbiology*; D054307:Enterotoxigenic Escherichia coli / Q000472:pathogenicity / Q000502:physiology*; D004768:Enterotoxins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins; D054884:Host-Pathogen Interactions; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050705:Receptors, Guanylate Cyclase-Coupled / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008024:Ligands; C034151:heat stable toxin (E coli); D050705:Receptors, Guanylate Cyclase-Coupled