6E8F

Crystal Structure of Human Protocadherin-15 EC3-5 CD2-1

6E8F の概要

• エントリーDOI: 10.2210/pdb6e8f/pdb
• 分子名称: Protocadherin-15, CALCIUM ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: mechanotransduction, calcium-binding protein, stereocilia, hair cell, tip link, cell adhesion
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 121786.90

構造登録者

Choudhary, D.,Tamilselvan, E.,Sotomayor, M. (登録日: 2018-07-29, 公開日: 2019-07-31, 最終更新日: 2024-10-09)

主引用文献

Choudhary, D.,Narui, Y.,Neel, B.L.,Wimalasena, L.N.,Klanseck, C.F.,De-la-Torre, P.,Chen, C.,Araya-Secchi, R.,Tamilselvan, E.,Sotomayor, M.
Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception.
Proc.Natl.Acad.Sci.USA, 2020

PubMed Abstract: The vertebrate inner ear, responsible for hearing and balance, is able to sense minute mechanical stimuli originating from an extraordinarily broad range of sound frequencies and intensities or from head movements. Integral to these processes is the tip-link protein complex, which conveys force to open the inner-ear transduction channels that mediate sensory perception. Protocadherin-15 and cadherin-23, two atypically large cadherins with 11 and 27 extracellular cadherin (EC) repeats, are involved in deafness and balance disorders and assemble as parallel homodimers that interact to form the tip link. Here we report the X-ray crystal structure of a protocadherin-15 + cadherin-23 heterotetrameric complex at 2.9-Å resolution, depicting a parallel homodimer of protocadherin-15 EC1-3 molecules forming an antiparallel complex with two cadherin-23 EC1-2 molecules. In addition, we report structures for 10 protocadherin-15 fragments used to build complete high-resolution models of the monomeric protocadherin-15 ectodomain. Molecular dynamics simulations and validated crystal contacts are used to propose models for the complete extracellular protocadherin-15 parallel homodimer and the tip-link bond. Steered molecular dynamics simulations of these models suggest conditions in which a structurally diverse and multimodal protocadherin-15 ectodomain can act as a stiff or soft gating spring. These results reveal the structural determinants of tip-link-mediated inner-ear sensory perception and elucidate protocadherin-15's structural and adhesive properties relevant in disease.

PubMed: 32963095
DOI: 10.1073/pnas.1920444117

実験手法

X-RAY DIFFRACTION (2.99 Å)