| Autor: |
Risør MW; Department of Molecular Biology and Genetics, Aarhus University , DK-8000 Aarhus, Denmark., Poulsen ET, Thomsen LR, Dyrlund TF, Nielsen TA, Nielsen NC, Sanggaard KW, Enghild JJ |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemistry [Biochemistry] 2014 Jun 17; Vol. 53 (23), pp. 3851-7. Date of Electronic Publication: 2014 Jun 06. |
| DOI: |
10.1021/bi401633w |
| Abstrakt: |
Human HtrA1 (high-temperature requirement protein A1) belongs to a conserved family of serine proteases involved in protein quality control and cell fate. The homotrimeric ubiquitously expressed protease has chymotrypsin-like specificity and primarily targets hydrophobic stretches in selected or misfolded substrate proteins. In addition, the enzyme is capable of exerting autolytic activity by removing the N-terminal insulin-like growth factor binding protein (IGFBP)/Kazal-like tandem motif without affecting the protease activity. In this study, we have addressed the mechanism governing the autolytic activity and find that it depends on the integrity of the disulfide bonds in the N-terminal IGFBP/Kazal-like domain. The specificity of the autolytic cleavage reveals a strong preference for cysteine in the P1 position of HtrA1, explaining the lack of autolysis prior to disulfide reduction. Significantly, the disulfides were reduced by thioredoxin, suggesting that autolysis of HtrA1 in vivo is linked to the endogenous redox balance and that the N-terminal domain acts as a redox-sensing switch. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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