Biology subjects

del Marmol, J.

Publications and source records attributed to del Marmol, J..

3 recordsLinked to original sources

bioRxiv2026

Structural basis for nutrient-activated channel opening in bacterial spore germination receptors

GerA-family germinant receptors were recently identified as ion channels that initiate germination of dormant bacterial spores in response to nutrients. Here we report 2.0-[A] cryo-electron microscopy structures of apo, agonist-bound, and antagonist-bound GerA, revealing a symmetric pentamer of heterotrimers. Signaling relies on two allosteric switches that radiate from the LeuT-type ligand-binding subunit in opposite directions, one away from the channel subunit and one directly toward it. A lipoprotein subunit reroutes the first switch and allosterically activates the second, promoting their convergence on the channel. Together, these rearrangements comprise a multipronged, cooperative signal transduction pathway that connects nutrient binding to pore opening in this new class of ligand-gated ion channels.

biophysics↗

bioRxiv2026

Assembly and Conformational Dynamics of Insect Odorant Receptors

Insects rely on odorant receptors (ORs), tetrameric ligand-gated ion channels, to detect and discriminate a wide range of chemical cues. Within the insect OR family, composed of hundreds of OR subtypes, a conserved subunit termed odorant receptor co-receptor (Orco) is present in insect olfactory neurons. While Orco and some ORs can assemble into homo-tetramers, odor-activated channels are hetero-tetramers comprising Orco and an odor-specific OR. Cryogenic electron microscopy (cryo-EM) structures from heterologous expression systems revealed that Orco and OR assembled with a 3:1 (Orco:OR) stoichiometry. In these complexes, the OR subunit is solely responsible for ligand-recognition, whereas the Orco subunits form the majority of the ion conduction pathway and are key for assembly and membrane trafficking. Because Orco and OR can assemble in diverse stoichiometries, of which Orco(4) and OR(4) homo-tetramers, as well as Orco(3)/OR(1) hetero-tetramers, have been experimentally documented, we sought to investigate assembly and conformational dynamics of insect Orco/OR complexes. Here, using high-speed atomic force microscopy (HS-AFM), unique in providing simultaneous structural and temporal resolution, we find that Orco/OR complexes can reversibly transition into stable non-tetrameric oligomeric states, such as trimers and pentamers, through membrane-diffusive oligomer exchange. Furthermore, while all cryo-EM structures showed a fourfold symmetric or pseudo-symmetric conformation, we observed that tetrameric assemblies frequently adopt a symmetry-broken 'pinched' configuration, in addition to the canonical symmetric 'square' arrangement. Notably, ligand-binding modulates the 'pinching' kinetics in Orco/OR hetero-tetramers. Overall, these findings reveal key aspects of assembly and conformational dynamics of the insect OR family.

biophysics↗

bioRxiv2021

The structural basis of odorant recognition in insect olfactory receptors

Olfactory systems must detect and discriminate an enormous diversity of chemicals in the environment. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors (ORs), thus allowing a finite number of receptors to detect an almost infinite chemical world. Although most individual ORs are sensitive to a variety of odorants, the structural basis for such flexible chemical recognition remains unknown. Here, we combine cryo-electron microscopy with functional studies of receptor tuning to gain insight into the structural and mechanistic basis of promiscuous odorant recognition. We show that OR5 from the jumping bristletail, Machilis hrabei, assembles as a homo-tetrameric odorant-gated ion channel with broad chemical tuning. We elucidated the structure of OR5 in multiple gating states, alone and in complex with two of its agonists--the odorant eugenol and the insect repellent DEET. Both ligands bind to a common binding site located in the transmembrane region of each subunit, composed of a simple geometric arrangement of aromatic and hydrophobic residues. We reveal that binding is mediated by hydrophobic, non-directional interactions with residues distributed throughout the binding pocket, enabling the flexible recognition of structurally distinct odorants. Mutation of individual residues lining the binding pocket predictably altered OR5s sensitivity to eugenol and DEET and broadly reconfigured the receptors tuning, supporting a model in which diverse odorants share the same structural determinants for binding. Together, these studies provide structural insight into odorant detection, shedding light onto the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.

neuroscience↗