Is mechanical receptor ligand dissociation driven by unfolding or unbinding?

ABSTRACTMechanical force can play a pivotal role in biological systems. Single Molecule Force Spectroscopy, is a powerful tool to probe the mechanics of proteins and their binding partners. Yet, it remains unclear how complex dissociation of a protein-protein interaction under mechanical forces occurs. Are receptor and ligand unbinding, or are they unfolding? We utilize an approach wherein receptor and ligand are expressed as a single molecule fused by a long flexible linker. Force is applied to the complex via an ultrastable handle. Consequently, the events during and following complex dissociation can be monitored. We investigate two high-affinity systems: The cohesin-dockerin type I interaction in which we find that a binding partner unfolds upon complex dissociation, and a colicin-immunity protein complex in which both proteins unfold completely upon unbinding. Mechanical receptor ligand dissociation thus can encompass unfolding of one or both binding partners.

G protein-mediated stretch reception

Mechanosensation and -transduction are important for physiological processes like the senses of touch, hearing, and balance. The mechanisms underlying the translation of mechanical stimuli into biochemical information by activating various signaling pathways play a fundamental role in physiology and pathophysiology but are only poorly understood. Recently, G protein-coupled receptors (GPCRs), which are essential for the conversion of light, olfactory and gustatory stimuli, as well as of primary messengers like hormones and neurotransmitters into cellular signals and which play distinct roles in inflammation, cell growth, and differentiation, have emerged as potential mechanosensors. The first candidate for a mechanosensitive GPCR was the angiotensin-II type-1 (AT1) receptor. Agonist-independent mechanical receptor activation of AT1 receptors induces an active receptor conformation that appears to differ from agonist-induced receptor conformations and entails the activation of G proteins. Mechanically induced AT1 receptor activation plays an important role for myogenic vasoconstriction and for the initiation of cardiac hypertrophy. A growing body of evidence suggests that other GPCRs are involved in mechanosensation as well. These findings highlight physiologically relevant, ligand-independent functions of GPCRs and add yet another facet to the polymodal activation spectrum of this ubiquitous protein family.

Some structural details of the hind wings detected in staphylinids of 7 subfamilies (Coleoptera)

Study of 41 species provided information as follows: (a) a setigerous lobe is located at the costal margin in every species in the subf. Staphylininae; (b) a setal comb occupies the same margin in Xantholinini and O maliinae; (c) one or more spinulae do line the anal fi eld of all O maliinae and most O xytelinae, Tachyporinae and A leocharinae; (d) number of these spinulae in A leocharinae ranges from 1 up to about 100 and is null in two species. Hypothetically, a functional importance may be attributed to both the setigerous lobe, which suggests a mechanical receptor for wing folding control, and to the flabellum-like anal fi eld of the Aleochara, which looks as a device affecting the flying trim.