8E51

Crystal Structure of Iridescent Shark Catfish Cadherin-23 EC1-2 and Protocadherin-15 EC1-2

Summary for 8E51

• Entry DOI: 10.2210/pdb8e51/pdb
• Descriptor: Protocadherin-15, Cadherin-23, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: hearing, deafness, cdh23, pcdh15, evolution, tip link, cell adhesion
• Biological source: Pangasianodon hypophthalmus (striped catfish); More
• Total number of polymer chains: 2
• Total formula weight: 53643.82

Authors

Scheib, E.,Nisler, C.R.,Sotomayor, M. (deposition date: 2022-08-19, release date: 2023-03-22, Last modification date: 2024-11-06)

Primary citation

Nisler, C.R.,Narui, Y.,Scheib, E.,Choudhary, D.,Bowman, J.D.,Mandayam Bharathi, H.,Lynch, V.J.,Sotomayor, M.
Interpreting the Evolutionary Echoes of a Protein Complex Essential for Inner-Ear Mechanosensation.
Mol.Biol.Evol., 40:-, 2023

PubMed Abstract: The sensory epithelium of the inner ear, found in all extant lineages of vertebrates, has been subjected to over 500 million years of evolution, resulting in the complex inner ear of modern vertebrates. Inner-ear adaptations are as diverse as the species in which they are found, and such unique anatomical variations have been well studied. However, the evolutionary details of the molecular machinery that is required for hearing are less well known. Two molecules that are essential for hearing in vertebrates are cadherin-23 and protocadherin-15, proteins whose interaction with one another acts as the focal point of force transmission when converting sound waves into electrical signals that the brain can interpret. This "tip-link" interaction exists in every lineage of vertebrates, but little is known about the structure or mechanical properties of these proteins in most non-mammalian lineages. Here, we use various techniques to characterize the evolution of this protein interaction. Results show how evolutionary sequence changes in this complex affect its biophysical properties both in simulations and experiments, with variations in interaction strength and dynamics among extant vertebrate lineages. Evolutionary simulations also characterize how the biophysical properties of the complex in turn constrain its evolution and provide a possible explanation for the increase in deafness-causing mutants observed in cadherin-23 relative to protocadherin-15. Together, these results suggest a general picture of tip-link evolution in which selection acted to modify the tip-link interface, although subsequent neutral evolution combined with varying degrees of purifying selection drove additional diversification in modern tetrapods.

PubMed: 36911992
DOI: 10.1093/molbev/msad057

Experimental method

X-RAY DIFFRACTION (2.594 Å)