ArticleThe Journal of biological chemistry2010
Cobra CRISP functions as an inflammatory modulator via a novel Zn2+- and heparan sulfate-dependent transcriptional regulation of endothelial cell adhesion molecules.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 96 citations in OpenAlex.
- Snake Toxins Affecting Blood Vessel Walls: Mode of Action and Biological Significance.International journal of molecular sciences · 2025Review
- Snake Venom Compounds: A New Frontier in the Battle Against Antibiotic-Resistant Infections.Toxins · 2025Review
- The C. elegans LON-1 protein requires its CAP domain for function in regulating body size and BMP signaling.Genetics · 2025Article
- Histopathological characterization of skin and muscle lesions induced by lionfish (The journal of venomous animals and toxins including tropical diseases · 2025Article
- Review
- Identification and Evolutionary Analysis of the Widely Distributed CAP Superfamily in Spider Venom.Toxins · 2024Article
- Article
- A member of the CAP protein superfamily, Hc-CAP-15, is important for the parasitic-stage development of Haemonchus contortus.Parasites & vectors · 2023Article
- The function of plant PR1 and other members of the CAP protein superfamily in plant-pathogen interactions.Molecular plant pathology · 2023Review
- An Emergent Role for Mitochondrial Bioenergetics in the Action of Snake Venom Toxins on Cancer Cells.Frontiers in oncology · 2022Review
- Article
- The less conserved metal-binding site in human CRISP1 remains sensitive to zinc ions to permit protein oligomerization.Scientific reports · 2021Article
- CRISPs Function to Boost Sperm Power Output and Motility.Frontiers in cell and developmental biology · 2021Article
- Proteomic Investigations of Two PakistaniToxins · 2020Article
- Regulation of Functional Protein Aggregation by Multiple Factors: Implications for the Amyloidogenic Behavior of the CAP Superfamily Proteins.International journal of molecular sciences · 2020Review
- Draft genome sequences of Hirudo medicinalis and salivary transcriptome of three closely related medicinal leeches.BMC genomics · 2020Article
- Article
- Review
- Article
- Patagonin-CRISP: Antimicrobial Activity and Source of Antimicrobial Molecules in Duvernoy's Gland Secretion (Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cysteine-rich secretory proteins (CRISPs) have been identified as a toxin family in most animal venoms with biological functions mainly associated with the ion channel activity of cysteine-rich domain (CRD). CRISPs also bind to Zn(2+) at their N-terminal pathogenesis-related (PR-1) domain, but their function remains unknown. Interestingly, similar the Zn(2+)-binding site exists in all CRISP family, including those identified in a wide range of organisms. Here, we report that the CRISP from Naja atra (natrin) could induce expression of vascular endothelial cell adhesion molecules, i.e. intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin, to promote monocytic cell adhesion in a heparan sulfate (HS)- and Zn(2+)-dependent manner. Using specific inhibitors and small interfering RNAs, the activation mechanisms are shown to involve both mitogen-activated protein kinases and nuclear factor-κB. Biophysical characterization of natrin by using fluorescence, circular dichroism, and x-ray crystallographic methods further reveals the presence of two Zn(2+)-binding sites for natrin. The strong binding site is located near the putative Ser-His-Glu catalytic triad of the N-terminal domain. The weak binding site remains to be characterized, but it may modulate HS binding by enhancing its interaction with long chain HS. Our results strongly suggest that natrin may serve as an inflammatory modulator that could perturb the wound-healing process of the bitten victim by regulating adhesion molecule expression in endothelial cells. Our finding uncovers a new aspect of the biological role of CRISP family in immune response and is expected to facilitate future development of new therapeutic strategy for the envenomed victims.
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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.