2KBQ

Solution structure of harmonin N terminal domain

2KBQ の概要

• エントリーDOI: 10.2210/pdb2kbq/pdb
• 関連するPDBエントリー: 2KBR 2KBS
• 分子名称: Harmonin (1 entity in total)
• 機能のキーワード: protein, alternative splicing, coiled coil, deafness, hearing, non-syndromic deafness, polymorphism, retinitis pigmentosa, sensory transduction, usher syndrome, vision, structural protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9567.10

構造登録者

Zhang, M.,Pan, L.,Yan, J.,Wu, L. (登録日: 2008-12-05, 公開日: 2009-03-31, 最終更新日: 2024-05-29)

主引用文献

Pan, L.,Yan, J.,Wu, L.,Zhang, M.
Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23
Proc.Natl.Acad.Sci.USA, 106:5575-5580, 2009

PubMed Abstract: The hereditary hearing-vision loss disease Usher syndrome (USH) is caused by defects in several proteins, most of which form an integrated protein network called Usher interactome. Harmonin/Ush1C is a master scaffold in the assembly of the Usher protein complexes, because harmonin is known to bind to every protein in the Usher interactome. However, the biochemical and structural mechanism governing the Usher protein complex formation is largely unclear. Here, we report that the highly-conserved N-terminal fragment of harmonin (N-domain) immediately preceding its PDZ1 adopts an autonomously-folded domain. We discovered that the N-domain specifically binds to a short internal peptide fragment of the cadherin 23 cytoplasmic domain. The structures of the harmonin N-domain alone and in complex with the cadherin 23 internal peptide fragment uncovered the detailed binding mechanism of this interaction between harmonin and cadherin 23. We further elucidated the harmonin PDZ domain-mediated cadherin 23 binding by solving the structure of the second harmonin PDZ domain in complex with the cadherin 23 carboxyl tail. The multidentate binding mode between harmonin and cadherin 23 provides a structural and biochemical basis for the harmonin-mediated assembly of stable tip link complex in the auditory hair cells.

PubMed: 19297620
DOI: 10.1073/pnas.0901819106

実験手法

SOLUTION NMR