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Phosphorylation of Cysteine string protein triggers a major conformational switch

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Phosphorylation of Cysteine string protein triggers a major conformational switch. / Patel, Pryank; Prescott, Gerald R.; Burgoyne, Robert D.; Lian, Lu-Yun; Morgan, Alan.

In: Structure, Vol. 24, No. 8, 02.08.2016, p. 1380-1386.

Research output: Contribution to journalArticlepeer-review

Harvard

Patel, P, Prescott, GR, Burgoyne, RD, Lian, L-Y & Morgan, A 2016, 'Phosphorylation of Cysteine string protein triggers a major conformational switch', Structure, vol. 24, no. 8, pp. 1380-1386. https://doi.org/10.1016/j.str.2016.06.009

APA

Patel, P., Prescott, G. R., Burgoyne, R. D., Lian, L-Y., & Morgan, A. (2016). Phosphorylation of Cysteine string protein triggers a major conformational switch. Structure, 24(8), 1380-1386. https://doi.org/10.1016/j.str.2016.06.009

Vancouver

Patel P, Prescott GR, Burgoyne RD, Lian L-Y, Morgan A. Phosphorylation of Cysteine string protein triggers a major conformational switch. Structure. 2016 Aug 2;24(8):1380-1386. https://doi.org/10.1016/j.str.2016.06.009

Author

Patel, Pryank ; Prescott, Gerald R. ; Burgoyne, Robert D. ; Lian, Lu-Yun ; Morgan, Alan. / Phosphorylation of Cysteine string protein triggers a major conformational switch. In: Structure. 2016 ; Vol. 24, No. 8. pp. 1380-1386.

Bibtex - Download

@article{1564fa15e1bf41ecb6db1f1af7fd8d62,
title = "Phosphorylation of Cysteine string protein triggers a major conformational switch",
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.",
keywords = "Adult onset neuronal lipofuscinosis, Chaperone, DnaJ, Hsp40, Neurodegeneration",
author = "Pryank Patel and Prescott, {Gerald R.} and Burgoyne, {Robert D.} and Lu-Yun Lian and Alan Morgan",
note = "This work was supported by a grant from the Wellcome Trust to A.M., L.Y.L., and R.D.B. (grant ref. 090077/Z/09/Z). G.R.P. was supported by a Wellcome Trust PhD studentship.",
year = "2016",
month = aug,
day = "2",
doi = "10.1016/j.str.2016.06.009",
language = "English",
volume = "24",
pages = "1380--1386",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "8",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Phosphorylation of Cysteine string protein triggers a major conformational switch

AU - Patel, Pryank

AU - Prescott, Gerald R.

AU - Burgoyne, Robert D.

AU - Lian, Lu-Yun

AU - Morgan, Alan

N1 - This work was supported by a grant from the Wellcome Trust to A.M., L.Y.L., and R.D.B. (grant ref. 090077/Z/09/Z). G.R.P. was supported by a Wellcome Trust PhD studentship.

PY - 2016/8/2

Y1 - 2016/8/2

N2 - 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.

AB - 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.

KW - Adult onset neuronal lipofuscinosis

KW - Chaperone

KW - DnaJ

KW - Hsp40

KW - Neurodegeneration

U2 - 10.1016/j.str.2016.06.009

DO - 10.1016/j.str.2016.06.009

M3 - Article

C2 - 27452402

VL - 24

SP - 1380

EP - 1386

JO - Structure

JF - Structure

SN - 0969-2126

IS - 8

ER -

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