2n04
From Proteopedia
Solution Structure of the phosphorylated N-terminal region of Human Cysteine String Protein (CSP)
Structural highlights
DiseaseDNJC5_HUMAN CLN4B disease. The disease is caused by mutations affecting the gene represented in this entry. FunctionDNJC5_HUMAN May have an important role in presynaptic function. May be involved in calcium-dependent neurotransmitter release at nerve endings (By similarity). Publication Abstract from PubMedCysteine 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 alpha 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. Phosphorylation of Cysteine String Protein Triggers a Major Conformational Switch.,Patel P, Prescott GR, Burgoyne RD, Lian LY, Morgan A Structure. 2016 Aug 2;24(8):1380-6. doi: 10.1016/j.str.2016.06.009. Epub 2016 Jul, 21. PMID:27452402[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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