ArticleThe Journal of biological chemistry2012
Enhancing integrin α1 inserted (I) domain affinity to ligand potentiates integrin α1β1-mediated down-regulation of collagen synthesis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Cortical Actin Depolymerisation in 3D Cell Culture Enhances Extracellular Vesicle Secretion and Therapeutic Effects.Journal of extracellular vesicles · 2025Article
- Integrins in the kidney - beyond the matrix.Nature reviews. Nephrology · 2025Review
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- The First Snake Venom KTS/Disintegrins-Integrin Interactions Using Bioinformatics Approaches.Molecules (Basel, Switzerland) · 2022Article
- The biological effect of recombinant humanized collagen on damaged skin induced by UV-photoaging: AnBioactive materials · 2022Article
- Magnesium Activates Microsecond Dynamics to Regulate Integrin-Collagen Recognition.Structure (London, England : 1993) · 2018Article
- Salt-bridge modulates differential calcium-mediated ligand binding to integrin α1- and α2-I domains.Scientific reports · 2018Article
- Intrinsic local destabilization of the C-terminus predisposes integrin α1 I domain to a conformational switch induced by collagen binding.Protein science : a publication of the Protein Society · 2016Article
- Surface biology of collagen scaffold explains blocking of wound contraction and regeneration of skin and peripheral nerves.Biomedical materials (Bristol, England) · 2015Review
- Chronic Wound Dressings Based on Collagen-Mimetic Proteins.Advances in wound care · 2015Article
- Integrin α1-null mice exhibit improved fatty liver when fed a high fat diet despite severe hepatic insulin resistance.The Journal of biological chemistry · 2015Article
- Endothelial cell response to chemical, biological, and physical cues in bioactive hydrogels.Tissue engineering. Part A · 2014Article
- Integrin-mediated type II TGF-β receptor tyrosine dephosphorylation controls SMAD-dependent profibrotic signaling.The Journal of clinical investigation · 2014Article
- The structure of integrin α1I domain in complex with a collagen-mimetic peptide.The Journal of biological chemistry · 2013Article
- Integrins in kidney disease.Journal of the American Society of Nephrology : JASN · 2013Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Integrin α1β1 binding to collagen IV, which is mediated by the α1-inserted (I) domain, down-regulates collagen synthesis. When unligated, a salt bridge between Arg(287) and Glu(317) is thought to keep this domain in a low affinity conformation. Ligand binding opens the salt bridge leading to a high-affinity conformation. How modulating integrin α1β1 affinity alters collagen homeostasis is unknown. To address this question, we utilized a thermolysin-derived product of the α1α2α1 network of collagen IV (α1α2α1(IV) truncated protomer) that selectively binds integrin α1β1. We show that an E317A substitution enhanced binding to the truncated protomer, consistent with a previous finding that this substitution eliminates the salt bridge. Surprisingly, we show that an R287A substitution did not alter binding, whereas R287E/E317R substitutions enhanced binding to the truncated protomer. NMR spectroscopy and molecular modeling suggested that eliminating the Glu(317) negative charge is sufficient to induce a conformational change toward the open state. Thus, the role played by Glu(317) is largely independent of the salt bridge. We further show that cells expressing E317A or R287E/E317R substitutions have enhanced down-regulation of collagen IV synthesis, which is mediated by the ERK/MAPK pathway. In conclusion, we have demonstrated that modulating the affinity of the extracellular α1 I domain to collagen IV enhances outside-in signaling by potentiating ERK activation and enhancing the down-regulation of collagen synthesis.
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Registered trials
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.