Cryo-EM structures reveal a dynamic transformation process of human alpha-2-macroglobulin working as a protease inhibitor

Huang, Xiaoxing; Wang, Youwang; Yu, Cong; Zhang, Hui; Ru, Qiang; Li, Xinxin; Song, Kai; Zhou, Min; Zhu, Ping

doi:10.1101/2022.05.10.491262

Cited by 3 publications

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

A single protein to multiple peptides: Investigation of protein-peptide relationship using targeted alpha-2-macroglobulin analysis

Yildiz

Özcan

2022

Preprint

View full text Add to dashboard Cite

Recent advances in proteomics technologies have enabled analysis of thousands of proteins in a high-throughput manner. Mass Spectrometry (MS) based proteomics, uses a peptide centric approach where biological samples undergo a specific proteolytic digestion and then only unique peptides are used for protein identification and quantification. Considering the fact that a single protein may have multiple unique peptides and a number of different forms, it becomes essential to understand dynamic protein-peptide relationship to ensure robust and reliable peptide centric protein analysis. In this study, we investigated the correlation between protein concentration and corresponding unique peptide responses under conventional proteolytic digestion conditions. Protein-peptide correlation, digestion efficiency, matrix-effect, and concentration-effect were evaluated. Twelve unique alpha-2-macroglobulin (A2MG) peptides were monitored using a targeted MS approach to acquire insights into protein-peptide dynamics. Although the peptide responses were reproducible between replicates, protein-peptide correlation was moderate in protein standards and low in complex matrices. The results suggest that reproducible peptide signal could be misleading in clinical studies and a peptide selection could dramatically change the outcome at protein level. This is the first study investigating quantitative protein-peptide correlations in biological samples using all unique peptides representing the same protein and opens a discussion on peptide-based proteomics.

show abstract

A single protein to multiple peptides: Investigation of protein-peptide relationship using targeted alpha-2-macroglobulin analysis

Yildiz

Özcan

2022

Preprint

View full text Add to dashboard Cite

show abstract

Antioxidative behavior of a2-macroglobulin in intervertebral disc degeneration

Chen¹,

Wei²,

Xu³

2023

J Med Biochemistry

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is one of the most common gynecological diseases that affect the fertility in women in Basra governorate. The current study was designed in order to assess iron aberrations in PCOS patients by measuring the related parameters and their relationship with sex hormones in patients with PCOS. Serum samples were collected from 45 PCOS patients and 45 controls from a private women’s clinic and were measured by ELISA in a private medical laboratory. The results showed a significant decrease in the level of hepcidin, transferrin and estradiol versus a significant increase in iron, ferritin, progesterone and testosterone. The current study showed a clear imbalance in the level of iron and its serum regulating parameters in in PCOS women, and there is an effective correlation between iron status and sex hormones.

show abstract

Antioxidative behavior of a2-macroglobulin in intervertebral disc degeneration

Chen¹,

Wei²,

Xu³

2023

J Med Biochemistry

View full text Add to dashboard Cite

Background: To clarify if α2-macroglobulin (α2M) has an antioxidative effect during the progression of the intervertebral disc degeneration (IVDD). Methods: The content of α2M and reactive oxygen species (ROS) were measured to compare mildly and severely degenerated human nucleus pulposus (NP) tissue by immunohistochemistry, mass spectrometry, and enzyme-linked immunosorbent assay (ELISA). Additionally, exogenic α2M was used to culture severely degenerated NP tissue in vitro. The effects of α2M on hypochlorite (HOCl)-treated NP cells were evaluated, containing antioxidative enzymes, ROS level, collagen II, and aggrecan expression, MMP3/13, and ADAMTS4/5. Results: ROS level increased in severely degenerated NP, accompanying with a decreased α2M content. Supplement of α2M could decrease the ROS level of cultured NP in vitro, meanwhile, the MMP13 and ADAMTS4 expression were also reduced. It was found that treatment of HOCl resulted in oxidative damage to NP cells and decreased α2M expression in a dose and time-dependent manner. Furthermore, exogenic α2M stimulation reversed the HOCl-triggered ROS accumulation. The promotion of SOD1/2, CAT, GPX1, collagen II, and aggrecan, and suppression of MMP3/13, ADAMTS4/5 expression caused by α2M were also observed. Conclusions: Our study indicates that α2M has an antioxidative ability in degenerated NP cells by promoting the antioxidative enzyme production.

show abstract

Cryo-EM structures reveal a dynamic transformation process of human alpha-2-macroglobulin working as a protease inhibitor

Cited by 3 publications

References 49 publications

A single protein to multiple peptides: Investigation of protein-peptide relationship using targeted alpha-2-macroglobulin analysis

A single protein to multiple peptides: Investigation of protein-peptide relationship using targeted alpha-2-macroglobulin analysis

Antioxidative behavior of a2-macroglobulin in intervertebral disc degeneration

Antioxidative behavior of a2-macroglobulin in intervertebral disc degeneration

Contact Info

Product

Resources

About