Human melanoma inhibitory protein binds to the FN12-14 Hep II domain of fibronectin

Abstract

The heparin binding site (Hep II) of fibronectin plays a major role in tumor cell metastasis. Its interaction with heparan sulfate proteoglycans occurs in a variety of physiological processes including focal adhesion and migration. The melanoma inhibitory activity (MIA) is an important protein that is functionally involved in melanoma development, progression, and tumor cell invasion. After its secretion by malignant melanoma cells, MIA interacts with fibronectin and thereby actively facilitates focal cell detachment from surrounding structures and strongly promotes tumor cell invasion and the formation of metastases. In this report, the authors have determined the molecular basis of the interaction of MIA with the Hep II domain of fibronectin based on nuclear magnetic resonance spectroscopic binding assays. The authors have identified the type III modules 12 to 14 of fibronectin's Hep II as the major MIA binding sites. These results now provide a new target protein-protein binding interface for the discovery of novel antimetastatic agents against malignant melanoma in the future.

Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos

“…Notably, proteins encoded by the mia gene family are involved in several processes involving the export or binding of bulky cargo, and are expressed in a diverse set of tissues. For instance, the extracellular MIA is found in cartilage and displays weak affinity to fibronectin III modules 30,31 . Similarly, Otoraplin is also found in cartilage, but specifically in the cochlea of murine embryos, without a known interaction partner, prior to this study [32][33][34] .…”

A Thermally Stable Recombinant Human Fibronectin Peptide-Fused Protein (rhFN3C) for Faster Aphthous Ulcer (AU) Healing

“…Growth factors are strongly involved in the wound-healing process [22]. FNIII12-14 contains the heparin-binding domain II and a highly intermixed growth factor-binding domain, which has been shown to exhibit strong affinity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor-beta (TGF-β) [23]. To achieve the best efficacy of FN-based fused protein, this peptide-fused protein should contain both the mentioned functional domains: one promoting cell adhesion and one promoting growth-factor binding.…”

Estimation of a stronger heparin binding locus in fibronectin domain III14using thermodynamics and molecular dynamics

“…Over the years, several reports have been published on biophysical studies of protein-heparin interaction. [12][13][14][15][16] Interactions of several peptides such as cell penetrating peptides (CPPs) have also been reported with heparin. [17][18][19][20][21] Since HEP II-heparin interactions can cause or exacerbates pathophysiological conditions, 22 there is a great prospect of developing agents that can block these interactions.…”