Analysis Biomolecular Interactions of OKT9-Fab for hTfR1 by BLI (CAT#: STEM-MB-0172-CJ)

Introduction

The human transferrin receptor (hTfR1), a single-pass transmembrane protein that regulates iron uptake into cells. Structural studies have determined the atomic nature of the interaction of Machupo virus (MACV) GP1 with hTfR1 and revealed a conserved binding site for clade B NWM GP1 binding on the apical domain of hTfR1. Recombinant monoclonal antibodies have been identified that exploit this vulnerability by binding hTfR1 and blocking the internalization of pseudotyped viral particles decorated with Junin (JUNV), Guanarito (GTOV), Sabiá (SABV), MACV, Chapare (CHAV), and Sabiá (SABV) virus glycoproteins (GP) but not pseudotyped viral particles expressing glycoproteins from Old World hemorrhagic fever viruses, such as Lassa virus (LASV). Such antibodies have been shown to block entry of the North American mammarenavirus AV96010151 into cells, expanding their potential efficacy against a broader spectrum of NWHF viruses. Likewise, arenacept, a recombinant protein consisting of the apical domain of hTfR1 fused to an Fc domain, is capable of binding GP1 of several NWMs and preventing pseudotyped virus internalization into cells. A concrete molecular basis for the inhibition of viral entry through hTfR1-targeting antibodies is still lacking. This is due in part to the absence of structures of these targeting agents bound to hTfR1 despite a large number being discovered and explored for other therapeutic applications. The murine monoclonal OKT9 was among the first antibodies shown to recognize hTfR1 in several cell lines and have its activity explored in a variety of contexts.