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Conserved Tryptophan residues in the Low-density lipoprotein receptor are essential for interactions with blood Coagulation factor VIII

Tuesday, October 09, 2012 — Poster Session I

1:00 p.m. – 3:00 p.m

Natcher Conference Center, Building 45




  • J.H. Kurasawa
  • S.A. Shestopal
  • E. Karnaukhova
  • E.B. Struble
  • T.K. Lee
  • A.G. Sarafanov


Low-density lipoprotein receptor (LDLR) is part of a family of endocytic receptors that binds and internalizes numerous ligands. It was shown that LDLR regulates the level of coagulation factor VIII (FVIII) in plasma (Bovenschen et al., 2005). The ligand binding sites of LDLR are located within a cluster of seven complement type repeats (CRs). Each CR was suggested to interact with a specific lysine on the ligand in a way that a conserved aromatic residue packs its side chain against the aliphatic portion of the lysine. (Fisher et al, 2006). Recently, we mapped a specific region of LDLR responsible for binding FVIII; in the present study we verified specificity of this interaction by site-directed mutagenesis of the receptor’s conserved tryptophan residues in this region. Upon mutating these residues into serines (Andersen et al, 2001), their binding to FVIII was significantly decreased. This data confirms specificity of these interactions, thus supports the mapping of the LDLR site for FVIII. Also, our study supports the general mode of ligand recognition by the LDLR family.

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