Plumieribetin, a fish lectin homologous to mannose-binding B-type lectins, inhibits the collagen-binding alpha1beta1 integrin.

Abstract

Recently, a few fish proteins have been described with a high homology to B-type lectins of monocotyledonous plants. Because of their mannose binding activity, they have been ascribed a role in innate immunity. By screening various fish venoms for their integrin inhibitory activity, we isolated a homologous protein from the fin stings and skin mucus of the scorpionfish (Scorpaena plumieri). This protein inhibits alpha1beta1 integrin binding to basement membrane collagen IV. By protein chemical and spectroscopic means, we demonstrated that this fish protein, called plumieribetin, is a homotetramer and contains a high content of anti-parallel beta strands, similar to the mannose-binding monocot B-lectins. It lacks both N-linked glycoconjugates and common O-glycan motifs. Despite its B-lectin-like structure, plumieribetin binds to alpha1beta1 integrin irrespective of N-glycosylation, suggesting a direct protein-protein interaction. This interaction is independent of divalent cations. On the cellular level, plumieribetin failed to completely detach hepatocarcinoma HepG2 cells and primary arterial smooth muscle cells from the collagen IV fragment CB3. However, plumieribetin weakened the cell-collagen contacts, reduced cell spreading, and altered the actin cytoskeleton, after the compensating alpha2beta1 integrin was blocked. The integrin inhibiting effect of plumieribetin adds a new function to the B-lectin family, which is known for pathogen defense.

• Authors: Karla de Santana Evangelista, Filipe Andrich, Flávia Figueiredo de Rezende, Stephan Niland, Marta N Cordeiro, Tim Horlacher, Riccardo Castelli, Alletta Schmidt-Hederich, Peter H Seeberger, Eladio F Sanchez, Michael Richardson, Suely Gomes de Figueiredo, Johannes A Eble
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 50 Pg. 34747-59 (Dec 11 2009) ISSN: 1083-351X [Electronic] United States
• PMID: 19850917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type IV
• Integrin alpha1beta1
• Lectins
• Venoms

Topics

• Amino Acid Sequence
• Animals
• Carbohydrate Conformation
• Carbohydrate Sequence
• Cell Adhesion (physiology)
• Cell Line
• Collagen Type IV (metabolism)
• Fishes
• Humans
• Integrin alpha1beta1 (metabolism)
• Lectins (chemistry, genetics, metabolism)
• Microarray Analysis
• Molecular Sequence Data
• Protein Conformation
• Sequence Alignment
• Venoms (chemistry)