Publication

The N terminus of the small heat shock protein HSPB7 drives its polyQ aggregation-suppressing activity

Wu, D., Vonk, J. J., Salles, F., Vonk, D., Haslbeck, M., Melki, R., Bergink, S. & Kampinga, H. H., 21-Jun-2019, In : The Journal of Biological Chemistry. 294, 25, p. 9985-9994 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Wu, D., Vonk, J. J., Salles, F., Vonk, D., Haslbeck, M., Melki, R., ... Kampinga, H. H. (2019). The N terminus of the small heat shock protein HSPB7 drives its polyQ aggregation-suppressing activity. The Journal of Biological Chemistry, 294(25), 9985-9994. https://doi.org/10.1074/jbc.RA118.007117

Author

Wu, Di ; Vonk, Jan J ; Salles, Felix ; Vonk, Danara ; Haslbeck, Martin ; Melki, Ronald ; Bergink, Steven ; Kampinga, Harm H. / The N terminus of the small heat shock protein HSPB7 drives its polyQ aggregation-suppressing activity. In: The Journal of Biological Chemistry. 2019 ; Vol. 294, No. 25. pp. 9985-9994.

Harvard

Wu, D, Vonk, JJ, Salles, F, Vonk, D, Haslbeck, M, Melki, R, Bergink, S & Kampinga, HH 2019, 'The N terminus of the small heat shock protein HSPB7 drives its polyQ aggregation-suppressing activity', The Journal of Biological Chemistry, vol. 294, no. 25, pp. 9985-9994. https://doi.org/10.1074/jbc.RA118.007117

Standard

The N terminus of the small heat shock protein HSPB7 drives its polyQ aggregation-suppressing activity. / Wu, Di; Vonk, Jan J; Salles, Felix; Vonk, Danara; Haslbeck, Martin; Melki, Ronald; Bergink, Steven; Kampinga, Harm H.

In: The Journal of Biological Chemistry, Vol. 294, No. 25, 21.06.2019, p. 9985-9994.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Wu D, Vonk JJ, Salles F, Vonk D, Haslbeck M, Melki R et al. The N terminus of the small heat shock protein HSPB7 drives its polyQ aggregation-suppressing activity. The Journal of Biological Chemistry. 2019 Jun 21;294(25):9985-9994. https://doi.org/10.1074/jbc.RA118.007117


BibTeX

@article{beb671a8f81e4497be0adf1eebf3c98b,
title = "The N terminus of the small heat shock protein HSPB7 drives its polyQ aggregation-suppressing activity",
abstract = "Heat shock protein family B (small) member 7 (HSPB7) is a unique, relatively unexplored member within the family of human small heat shock proteins (HSPBs). Unlike most HSPB family members, HSPB7 does not oligomerize and so far has not been shown to associate with any other member of the HSPB family. Intriguingly, it was found to be the most potent member within the HSPB family to prevent aggregation of proteins with expanded polyglutamine (polyQ) stretches. How HSPB7 suppresses polyQ aggregation has remained elusive so far. Here, using several experimental strategies, including in vitroaggregation assays and immunoblotting and -fluorescence approaches, we show that the polyQ aggregation-inhibiting activity of HSPB7 is fully dependent on its flexible N-terminal domain (NTD). We observed that the NTD of HSPB7 is both required for association with and inhibition of polyQ aggregation. Remarkably, replacing the NTD of HSPB1, which itself cannot suppress polyQ aggregation, with the NTD of HSPB7 resulted in a hybrid protein that gained anti-polyQ aggregation activity. The hybrid NTDHSPB7-HSPB1 protein displayed a reduction in oligomer size and, unlike wildtype HSPB1, associated with polyQ. However, experiments with phospho-mimicking HSPB1 mutants revealed that de-oligomerization of HSPB1 alone does not suffice to gain polyQ aggregation-inhibiting activity. Together, our results reveal that the NTD of HSPB7 is both necessary and sufficient to bind to and suppress the aggregation of polyQ-containing proteins.",
author = "Di Wu and Vonk, {Jan J} and Felix Salles and Danara Vonk and Martin Haslbeck and Ronald Melki and Steven Bergink and Kampinga, {Harm H}",
note = "Published under license by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2019",
month = "6",
day = "21",
doi = "10.1074/jbc.RA118.007117",
language = "English",
volume = "294",
pages = "9985--9994",
journal = "The Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC",
number = "25",

}

RIS

TY - JOUR

T1 - The N terminus of the small heat shock protein HSPB7 drives its polyQ aggregation-suppressing activity

AU - Wu, Di

AU - Vonk, Jan J

AU - Salles, Felix

AU - Vonk, Danara

AU - Haslbeck, Martin

AU - Melki, Ronald

AU - Bergink, Steven

AU - Kampinga, Harm H

N1 - Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2019/6/21

Y1 - 2019/6/21

N2 - Heat shock protein family B (small) member 7 (HSPB7) is a unique, relatively unexplored member within the family of human small heat shock proteins (HSPBs). Unlike most HSPB family members, HSPB7 does not oligomerize and so far has not been shown to associate with any other member of the HSPB family. Intriguingly, it was found to be the most potent member within the HSPB family to prevent aggregation of proteins with expanded polyglutamine (polyQ) stretches. How HSPB7 suppresses polyQ aggregation has remained elusive so far. Here, using several experimental strategies, including in vitroaggregation assays and immunoblotting and -fluorescence approaches, we show that the polyQ aggregation-inhibiting activity of HSPB7 is fully dependent on its flexible N-terminal domain (NTD). We observed that the NTD of HSPB7 is both required for association with and inhibition of polyQ aggregation. Remarkably, replacing the NTD of HSPB1, which itself cannot suppress polyQ aggregation, with the NTD of HSPB7 resulted in a hybrid protein that gained anti-polyQ aggregation activity. The hybrid NTDHSPB7-HSPB1 protein displayed a reduction in oligomer size and, unlike wildtype HSPB1, associated with polyQ. However, experiments with phospho-mimicking HSPB1 mutants revealed that de-oligomerization of HSPB1 alone does not suffice to gain polyQ aggregation-inhibiting activity. Together, our results reveal that the NTD of HSPB7 is both necessary and sufficient to bind to and suppress the aggregation of polyQ-containing proteins.

AB - Heat shock protein family B (small) member 7 (HSPB7) is a unique, relatively unexplored member within the family of human small heat shock proteins (HSPBs). Unlike most HSPB family members, HSPB7 does not oligomerize and so far has not been shown to associate with any other member of the HSPB family. Intriguingly, it was found to be the most potent member within the HSPB family to prevent aggregation of proteins with expanded polyglutamine (polyQ) stretches. How HSPB7 suppresses polyQ aggregation has remained elusive so far. Here, using several experimental strategies, including in vitroaggregation assays and immunoblotting and -fluorescence approaches, we show that the polyQ aggregation-inhibiting activity of HSPB7 is fully dependent on its flexible N-terminal domain (NTD). We observed that the NTD of HSPB7 is both required for association with and inhibition of polyQ aggregation. Remarkably, replacing the NTD of HSPB1, which itself cannot suppress polyQ aggregation, with the NTD of HSPB7 resulted in a hybrid protein that gained anti-polyQ aggregation activity. The hybrid NTDHSPB7-HSPB1 protein displayed a reduction in oligomer size and, unlike wildtype HSPB1, associated with polyQ. However, experiments with phospho-mimicking HSPB1 mutants revealed that de-oligomerization of HSPB1 alone does not suffice to gain polyQ aggregation-inhibiting activity. Together, our results reveal that the NTD of HSPB7 is both necessary and sufficient to bind to and suppress the aggregation of polyQ-containing proteins.

U2 - 10.1074/jbc.RA118.007117

DO - 10.1074/jbc.RA118.007117

M3 - Article

C2 - 31097540

VL - 294

SP - 9985

EP - 9994

JO - The Journal of Biological Chemistry

JF - The Journal of Biological Chemistry

SN - 0021-9258

IS - 25

ER -

ID: 83111624