TIMP-3 facilitates binding of target metalloproteinases to the endocytic receptor LRP-1 and promotes scavenging of MMP-1.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
21 07 2020
Historique:
received: 22 01 2020
accepted: 06 07 2020
entrez: 23 7 2020
pubmed: 23 7 2020
medline: 22 12 2020
Statut: epublish

Résumé

Matrix metalloproteinases (MMPs) and the related families of disintegrin metalloproteinases (ADAMs) and ADAMs with thrombospondin repeats (ADAMTSs) play a crucial role in extracellular matrix (ECM) turnover and shedding of cell-surface molecules. The proteolytic activity of metalloproteinases is post-translationally regulated by their endogenous inhibitors, known as tissue inhibitors of metalloproteinases (TIMPs). Several MMPs, ADAMTSs and TIMPs have been reported to be endocytosed by the low-density lipoprotein receptor-related protein-1 (LRP-1). Different binding affinities of these proteins for the endocytic receptor correlate with different turnover rates which, together with differences in their mRNA expression, determines their nett extracellular levels. In this study, we used surface plasmon resonance to evaluate the affinity between LRP-1 and a number of MMPs, ADAMs, ADAMTSs, TIMPs and metalloproteinase/TIMP complexes. This identified MMP-1 as a new LRP-1 ligand. Among the proteins analyzed, TIMP-3 bound to LRP-1 with highest affinity (K

Identifiants

pubmed: 32694578
doi: 10.1038/s41598-020-69008-9
pii: 10.1038/s41598-020-69008-9
pmc: PMC7374751
doi:

Substances chimiques

LRP1 protein, human 0
Low Density Lipoprotein Receptor-Related Protein-1 0
Multiprotein Complexes 0
TIMP3 protein, human 0
Tissue Inhibitor of Metalloproteinase-3 0
Matrix Metalloproteinases EC 3.4.24.-
Matrix Metalloproteinase 1 EC 3.4.24.7

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12067

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Auteurs

Anna P Carreca (AP)

Department of Research, Fondazione Ri.MED - ISMETT, Via Ernesto Tricomi 5, 90145, Palermo, Italy.

Veronica M Pravatà (VM)

Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.

Matthew Markham (M)

Norwich Medical School, University of East Anglia, Norwich, NR4 7UQ, UK.

Simone Bonelli (S)

Department of Research, Fondazione Ri.MED - ISMETT, Via Ernesto Tricomi 5, 90145, Palermo, Italy.

Gillian Murphy (G)

Li Ka Shing Centre, Cancer Research UK, Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.

Hideaki Nagase (H)

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Headington, Oxford, UK.

Linda Troeberg (L)

Norwich Medical School, University of East Anglia, Norwich, NR4 7UQ, UK.

Simone D Scilabra (SD)

Department of Research, Fondazione Ri.MED - ISMETT, Via Ernesto Tricomi 5, 90145, Palermo, Italy. sdscilabra@fondazionerimed.com.

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