PDBsum entry 6eet

Cell adhesion

PDB id: 6eet

Contents

Protein chain

443 a.a.

Ligands

NAG-NAG ×2

MAN ×3

EPE

Metals

_CA ×4

PDB id:

6eet

Name:

Cell adhesion

Title:

Crystal structure of mouse protocadherin-15 ec9-mad12

Structure:

Protocadherin-15. Chain: a. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: pcdh15. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: expi293.

Resolution:

3.23Å R-factor: 0.179 R-free: 0.234

Authors:

Y.Narui,M.Sotomayor

Key ref:

D.Choudhary et al. (2020). Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception. Proc Natl Acad Sci U S A, 117, 24837-24848. PubMed id: 32963095 DOI: 10.1073/pnas.1920444117

Date:

15-Aug-18 Release date: 21-Aug-19

Protein chain

Q99PJ1  (PCD15_MOUSE) -  Protocadherin-15 from Mus musculus

Seq: 1943 a.a.

Struc: 443 a.a.

DOI no: 10.1073/pnas.1920444117

Proc Natl Acad Sci U S A 117:24837-24848 (2020)

PubMed id: 32963095

Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception.

D.Choudhary, Y.Narui, B.L.Neel, L.N.Wimalasena, C.F.Klanseck, P.De-la-Torre, C.Chen, R.Araya-Secchi, E.Tamilselvan, M.Sotomayor.

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.