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

doi:10.1110/ps.0219802

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

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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 and Lijun Rong

Protein science, Vol.11(11), pp.2596-2605

11/2002

DOI: 10.1110/ps.0219802

PMCID: PMC2373729

PMID: 12381843

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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.

protein folding

LDL-A module

familial hypercholesterolemia (FH)

Tva

Details

Title: Subtitle: Characterization of the LDL-A module mutants of Tva, the subgroup A Rous sarcoma virus receptor, and the implications in protein folding
Creators: Qing-Yin Wang - Department of Microbiology and Immunology
Balaji Manicassamy - Department of Microbiology and Immunology
Xuemei Yu - Department of Microbiology and Immunology
Klavs Dolmer - Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA
Peter G.W Gettins - Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA
Lijun Rong - Department of Microbiology and Immunology
Resource Type: Journal article
Publication Details: Protein science, Vol.11(11), pp.2596-2605
Publisher: Cold Spring Harbor Laboratory Press
DOI: 10.1110/ps.0219802
PMID: 12381843
PMCID: PMC2373729
ISSN: 0961-8368
eISSN: 1469-896X
Language: English
Date published: 11/2002
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083300002771

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