The sensing of bacteria: emerging principles for the detection of signal sequences by formyl peptide receptors.
The ability to detect specific chemical signatures released by bacteria and other microorganisms is a fundamental feature of immune defense against pathogens. There is increasing evidence that chemodetection of such microorganism-associated molecular patterns (MAMPs) occurs at many places in the body including specific sets of chemosensory neurons in the mammalian nose. Formyl peptide receptors (FPRs) are a unique family of G protein-coupled receptors (GPCRs) that can detect the presence of bacteria and function as chemotactic receptors. Here, we highlight the recent discovery of a vast family of natural FPR agonists, the bacterial signal peptides (or signal sequences), thus providing new insight into the molecular mechanisms of bacterial sensing by human and mouse FPRs. Signal peptides in bacteria are formylated, N-terminal protein signatures required for directing the transfer of proteins through the plasma membrane. After their cleavage and release, signal peptides are available for FPR detection and thus provide a previously unrecognized MAMP. With over 170 000 predicted sequences, bacterial signal peptides represent one of the largest families of GPCR ligands and one of the most complex classes of natural activators of the innate immune system. By recognizing a conserved three-dimensional peptide motif, FPRs employ an unusual detection mechanism that combines structural promiscuity with high specificity and sensitivity, thus solving the problem of detecting thousands of distinct sequences yet maintaining selectivity. How signal peptides are released by bacteria and sensed by GPCRs and how these processes shape the responses of other cells and whole organisms represents an important topic for future research.
Bernd
B
Bufe
Frank
F
Zufall
D020816:Amino Acid Motifs; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018407:Bacterial Physiological Phenomena; D002628:Chemoreceptor Cells / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D021382:Protein Sorting Signals; D021381:Protein Transport; D044042:Receptors, Formyl Peptide / Q000819:agonists / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
D021382:Protein Sorting Signals; D044042:Receptors, Formyl Peptide