Characterization of the LDL-A module mutants of Tva, the subgroup A Rous sarcoma virus receptor, and the implications in protein folding

Qing Yin Wang, Balaji Manicassamy, Xuemei Yu, Klavs Dolmer, Peter G.W. Gettins, Lijun Rong

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Tva is the cellular receptor for subgroup A Rous sarcoma virus (RSV-A), and the viral receptor function is solely determined by a 40-residue motif called the LDL-A module of Tva. In this report, an integral approach of molecular, biochemical, and biophysical techniques was used to examine the role of a well-conserved tryptophan of the LDL-A module of Tva in protein folding and ligand binding. We show that substitution of tryptophan by glycine adversely affected the correct folding of the LDL-A module of Tva, with only a portion giving a calcium-binding conformation. Furthermore, we show that the misfolded LDL-A conformations of Tva could not efficiently bind to its ligand. These results indicate that this conserved tryptophan in the LDL-A module of Tva plays an important role in correct protein folding and ligand recognition. Furthermore, these results suggest that the familial hypercholesterolemia (FH) French Canadian-4 mutation is likely caused by protein misfolding of low-density lipoprotein receptor, thus explaining the defect for this class of FH.

Original languageEnglish
Pages (from-to)2596-2605
Number of pages10
JournalProtein Science
Volume11
Issue number11
DOIs
StatePublished - Nov 2002
Externally publishedYes

Keywords

  • Familial hypercholesterolemia (FH)
  • LDL-A module
  • Protein folding
  • Tva

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