Evidence map›Paper›PMID 33580179›Full record

ArticleCommunications biology2021

pH-dependent and dynamic interactions of cystatin C with heparan sulfate.

Xiaoxiao Zhang, Xinyue Liu, Guowei Su, Miaomiao Li, Jian Liu, Chunyu Wang, Ding Xu

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Heparan sulfate selectively inhibits the collagenase activity of cathepsin K.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Heparan sulfate promotes TRAIL-induced tumor cell apoptosis.bioRxiv : the preprint server for biology · 2023
    Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Xiaoxiao Zhang *Department of Oral Biology, The University at Buffalo, Buffalo, NY, USA.ORCID 0000-0003-1321-0798
Xinyue Liu *Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Guowei SuDivision of Chemical Biology and Natural Product, School of Pharmacy, The University of North Carolina, Chapel Hill, NC, USA.
Miaomiao LiDepartment of Oral Biology, The University at Buffalo, Buffalo, NY, USA.
Jian LiuDivision of Chemical Biology and Natural Product, School of Pharmacy, The University of North Carolina, Chapel Hill, NC, USA.
Chunyu WangDepartment of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. wangc5@rpi.edu.ORCID 0000-0001-5165-7959
Ding XuDepartment of Oral Biology, The University at Buffalo, Buffalo, NY, USA. dingxu@buffalo.edu.ORCID 0000-0001-9380-2712
University at Buffalo, State University of New York · USRensselaer Polytechnic Institute · USUniversity of North Carolina at Chapel Hill · US

Funding

In vitro synthesis of recombinant heparan sulfateR01HL094463 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, JIAN, PAWLINSKI, RAFAL L · 2009 to 2021
$5.2M
Heparan Sulfate 3-O-Sulfation in Transcellular Propagation of Tauopathy in Alzheimer's DiseaseRF1AG069039 · NIA · RENSSELAER POLYTECHNIC INSTITUTE · PI LINHARDT, ROBERT J, LIU, JIAN · 2020 to 2020
$2.6M
Developing Heparan Sulfate Glycan ArrayR44GM123792 · NIGMS · GLYCAN THERAPEUTICS CORPORATION · PI SU, GUOWEI · 2020 to 2021
$2.4M
Heparan Sulfate–Osteoprotegerin Interactions in Bone RemodelingR01AR070179 · NIAMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI XU, DING · 2017 to 2021
$1.7M
Predoctoral Training Program for Alzheimer’s Disease at the Interface of Data Science, Engineering and BiologyT32AG078123 · NIA · RENSSELAER POLYTECHNIC INSTITUTE · PI Chunyu Wang · 2023 to 2026
$974k
Synthesis and Pharmacological Evaluation of Homogenous Ultra-Low Molecular Weight HeparinsR01HL144970 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, JIAN · 2019 to 2021
$946k
NHLBI NIH HHS R01 HL094463NHLBI NIH HHS R01 HL144970NIAMS NIH HHS R01 AR070179NIA NIH HHS RF1 AG069039NIA NIH HHS T32 AG078123NIGMS NIH HHS R44 GM123792
6 · The paper itself

Abstract

Cystatin C (Cst-3) is a potent inhibitor of cysteine proteases with diverse biological functions. As a secreted protein, the potential interaction between Cst-3 and extracellular matrix components has not been well studied. Here we investigated the interaction between Cst-3 and heparan sulfate (HS), a major component of extracellular matrix. We discovered that Cst-3 is a HS-binding protein only at acidic pH. By NMR and site-directed mutagenesis, we identified two HS binding regions in Cst-3: the highly dynamic N-terminal segment and a flexible region located between residue 70-94. The composition of the HS-binding site by two highly dynamic halves is unique in known HS-binding proteins. We further discovered that HS-binding severely impairs the inhibitory activity of Cst-3 towards papain, suggesting the interaction could actively regulate Cst-3 activity. Using murine bone tissues, we showed that Cst-3 interacts with bone matrix HS at low pH, again highlighting the physiological relevance of our discovery.

Indexed as

AnimalsBinding SitesCell LineCystatin CExtracellular MatrixFemurHeparan SulfateHydrogen-Ion ConcentrationMaleMiceMutagenesis, Site-DirectedMutationPapainProtein BindingProton Magnetic Resonance SpectroscopyCst3 protein, mouseCystatin CHeparan SulfatePapain

Identifiers

PMID33580179
PMCPMC7881039
OpenAlexW3128755942

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.