Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Deadly Spiders & Scary Zombies - NOT a Halloween Story
A near atomic resolution glance into the CNS

Synapses are specialized junctions between neurons that transmit and compute information in the central nervous system (CNS). The establishment, properties, and dynamics of synapses are governed by diverse trans-synaptic signaling molecules that communicate their signal via multifarious interactions with their synaptic partners. Mutations in the genes encoding these molecules have been associated with diverse neuropsychiatric and neurodegenerative disorders thus highlighting their crucial importance for normal brain function. Over the past few decades, tremendous efforts have been made to structurally characterize the trans-synaptic signaling molecules as well as their interacting partners. Nevertheless, their low expression levels and high structural complexity has posed a great challenge to traditional structural methods, such as NMR and X-ray crystallography. Advances in single particle electron cryo-microscopy (cryo-EM) now allow the capture of such complexed macromolecular assemblies in great details, providing snapshots of these fascinating molecules in action. Here we present the near atomic resolution structures of two such synaptic components, the cannabinoid receptor 1 (CB1R), and teneurin, two transmembrane receptors that are primarily expressed in neurons and are considered to mediate various functions in synapse formation and maintenance. The structures provide a high-resolution glance into the receptors’ architectures and present structural insights into the interaction with their inter- and intra- cellular partners. Our results highlight cryo-EM as a highly effective alternative approach for studying challenging macromolecular machineries while providing a framework for elucidating the mechanisms of action of trans-synaptic signaling molecules that could in turn be used for design of future novel therapeutics.

Moran Shalev-Benami

Department of Structural Biology,
Weizmann Institute of Science
Rehovot, Israel 7610001

Email: moransb@weizmann.ac.il