2N04

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

Summary for 2N04

• Entry DOI: 10.2210/pdb2n04/pdb
• NMR Information: BMRB: 25514
• Descriptor: DnaJ homolog subfamily C member 5 (1 entity in total)
• Functional Keywords: phosphorylation, dnaj, chaperone
• Biological source: Homo sapiens (human)
• Cellular location: Membrane ; Lipid-anchor : Q9H3Z4
• Total number of polymer chains: 1
• Total formula weight: 11984.20

Authors

Patel, P.,Lian, L.,Morgan, A.,Burgoyne, R. (deposition date: 2015-03-04, release date: 2016-07-13, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

SOLUTION NMR