2N04

Solution Structure of the phosphorylated N-terminal region of Human Cysteine String Protein (CSP)

2N04 の概要

• エントリーDOI: 10.2210/pdb2n04/pdb
• NMR情報: BMRB: 25514
• 分子名称: DnaJ homolog subfamily C member 5 (1 entity in total)
• 機能のキーワード: phosphorylation, dnaj, chaperone
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane ; Lipid-anchor : Q9H3Z4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11984.20

構造登録者

Patel, P.,Lian, L.,Morgan, A.,Burgoyne, R. (登録日: 2015-03-04, 公開日: 2016-07-13, 最終更新日: 2024-11-20)

主引用文献

Patel, P.,Prescott, G.R.,Burgoyne, R.D.,Lian, L.Y.,Morgan, A.
Phosphorylation of Cysteine String Protein Triggers a Major Conformational Switch.
Structure, 24:1380-1386, 2016

PubMed Abstract: Cysteine string protein (CSP) is a member of the DnaJ/Hsp40 chaperone family that localizes to neuronal synaptic vesicles. Impaired CSP function leads to neurodegeneration in humans and model organisms as a result of misfolding of client proteins involved in neurotransmission. Mammalian CSP is phosphorylated in vivo on Ser10, and this modulates its protein interactions and effects on neurotransmitter release. However, there are no data on the structural consequences of CSP phosphorylation to explain these functional effects. We show that Ser10 phosphorylation causes an order-to-disorder transition that disrupts CSP's extreme N-terminal α helix. This triggers the concomitant formation of a hairpin loop stabilized by ionic interactions between phosphoSer10 and the highly conserved J-domain residue, Lys58. These phosphorylation-induced effects result in significant changes to CSP conformation and surface charge distribution. The phospho-switch revealed here provides structural insight into how Ser10 phosphorylation modulates CSP function and also has potential implications for other DnaJ phosphoproteins.

PubMed: 27452402
DOI: 10.1016/j.str.2016.06.009

実験手法

SOLUTION NMR