7n4p

From Proteopedia

Crystal Structure of Lizard Cadherin-23 EC1-2

Structural highlights

7n4p is a 1 chain structure with sequence from Anolis carolinensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.097Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

R4GAX0_ANOCA

Publication Abstract from PubMed

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 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, while subsequent neutral evolution combined with varying degrees of purifying selection drove additional diversification in modern tetrapods.

Interpreting the Evolutionary Echoes of a Protein Complex Essential for Inner-Ear Mechanosensation.,Nisler CR, Narui Y, Scheib E, Choudhary D, Bowman JD, Mandayam Bharathi H, Lynch VJ, Sotomayor M Mol Biol Evol. 2023 Mar 13:msad057. doi: 10.1093/molbev/msad057. PMID:36911992^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nisler CR, Narui Y, Scheib E, Choudhary D, Bowman JD, Mandayam Bharathi H, Lynch VJ, Sotomayor M. Interpreting the Evolutionary Echoes of a Protein Complex Essential for Inner-Ear Mechanosensation. Mol Biol Evol. 2023 Apr 4;40(4):msad057. PMID:36911992 doi:10.1093/molbev/msad057