A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies

Christian Mumenthaler, Urs Schneider, Christian J. Buchholz, Daniel Koller, Werner Braun, Roberto Cattaneo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The two terminal complement control protein (CCP) modules of the CD46 glycoprotein mediate measles virus binding. Three-dimensional models for these two domains were derived based on the NMR structures of two CCP modules of factor H. Both CD46 CCP modules are about 35 Å long, and form a five- stranded antiparallel/β-barrel structure. Monte Carlo simulations, sampling the backbone torsion angles of the linker peptide and selecting possible orientations on the basis of minimal solvent-exposed hydrophobic area, were used to predict the orientation of CCP-I relative to CCP-II. We tested this procedure successfully for factor H. For CD46, three clusters of structures differing in the tilt angle of the two domains were obtained. To test these models, we mutagenized the CCP modules. Four proteins, two without an oligosaccharide chain and two with mutated short amino acid segments, reached the cell surface efficiently. Only the protein without the CCP-I oligosaccharide chain maintained binding to the viral attachment protein hemagglutinin. These results are consistent with one of our models and suggest that the vital hemagglutinin does not bind at the membrane-distal tip of CD46, but near the concave CCP-I-II interface region.

Original languageEnglish (US)
Pages (from-to)588-597
Number of pages10
JournalProtein Science
Volume6
Issue number3
StatePublished - Mar 1997
Externally publishedYes

Fingerprint

Virus Receptors
Measles virus
Hemagglutinins
Complement System Proteins
Proteins
Complement Factor H
Oligosaccharides
Virus Attachment
Monte Carlo simulation
Viral Proteins
Glycoproteins
Viruses
Torsional stress
Amino Acids
Peptides
Membranes

Keywords

  • complement control protein module
  • distance geometry
  • FANTOM
  • hemagglutinin binding
  • hydrophobic solvent-accessible surface area
  • measles virus receptor CD46
  • module assembly
  • Monte Carlo simulations

ASJC Scopus subject areas

  • Biochemistry

Cite this

A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies. / Mumenthaler, Christian; Schneider, Urs; Buchholz, Christian J.; Koller, Daniel; Braun, Werner; Cattaneo, Roberto.

In: Protein Science, Vol. 6, No. 3, 03.1997, p. 588-597.

Research output: Contribution to journalArticle

Mumenthaler, Christian ; Schneider, Urs ; Buchholz, Christian J. ; Koller, Daniel ; Braun, Werner ; Cattaneo, Roberto. / A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies. In: Protein Science. 1997 ; Vol. 6, No. 3. pp. 588-597.
@article{dea050491e3d4af89a7a0c9758d32e43,
title = "A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies",
abstract = "The two terminal complement control protein (CCP) modules of the CD46 glycoprotein mediate measles virus binding. Three-dimensional models for these two domains were derived based on the NMR structures of two CCP modules of factor H. Both CD46 CCP modules are about 35 {\AA} long, and form a five- stranded antiparallel/β-barrel structure. Monte Carlo simulations, sampling the backbone torsion angles of the linker peptide and selecting possible orientations on the basis of minimal solvent-exposed hydrophobic area, were used to predict the orientation of CCP-I relative to CCP-II. We tested this procedure successfully for factor H. For CD46, three clusters of structures differing in the tilt angle of the two domains were obtained. To test these models, we mutagenized the CCP modules. Four proteins, two without an oligosaccharide chain and two with mutated short amino acid segments, reached the cell surface efficiently. Only the protein without the CCP-I oligosaccharide chain maintained binding to the viral attachment protein hemagglutinin. These results are consistent with one of our models and suggest that the vital hemagglutinin does not bind at the membrane-distal tip of CD46, but near the concave CCP-I-II interface region.",
keywords = "complement control protein module, distance geometry, FANTOM, hemagglutinin binding, hydrophobic solvent-accessible surface area, measles virus receptor CD46, module assembly, Monte Carlo simulations",
author = "Christian Mumenthaler and Urs Schneider and Buchholz, {Christian J.} and Daniel Koller and Werner Braun and Roberto Cattaneo",
year = "1997",
month = "3",
language = "English (US)",
volume = "6",
pages = "588--597",
journal = "Protein Science",
issn = "0961-8368",
publisher = "Cold Spring Harbor Laboratory Press",
number = "3",

}

TY - JOUR

T1 - A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies

AU - Mumenthaler, Christian

AU - Schneider, Urs

AU - Buchholz, Christian J.

AU - Koller, Daniel

AU - Braun, Werner

AU - Cattaneo, Roberto

PY - 1997/3

Y1 - 1997/3

N2 - The two terminal complement control protein (CCP) modules of the CD46 glycoprotein mediate measles virus binding. Three-dimensional models for these two domains were derived based on the NMR structures of two CCP modules of factor H. Both CD46 CCP modules are about 35 Å long, and form a five- stranded antiparallel/β-barrel structure. Monte Carlo simulations, sampling the backbone torsion angles of the linker peptide and selecting possible orientations on the basis of minimal solvent-exposed hydrophobic area, were used to predict the orientation of CCP-I relative to CCP-II. We tested this procedure successfully for factor H. For CD46, three clusters of structures differing in the tilt angle of the two domains were obtained. To test these models, we mutagenized the CCP modules. Four proteins, two without an oligosaccharide chain and two with mutated short amino acid segments, reached the cell surface efficiently. Only the protein without the CCP-I oligosaccharide chain maintained binding to the viral attachment protein hemagglutinin. These results are consistent with one of our models and suggest that the vital hemagglutinin does not bind at the membrane-distal tip of CD46, but near the concave CCP-I-II interface region.

AB - The two terminal complement control protein (CCP) modules of the CD46 glycoprotein mediate measles virus binding. Three-dimensional models for these two domains were derived based on the NMR structures of two CCP modules of factor H. Both CD46 CCP modules are about 35 Å long, and form a five- stranded antiparallel/β-barrel structure. Monte Carlo simulations, sampling the backbone torsion angles of the linker peptide and selecting possible orientations on the basis of minimal solvent-exposed hydrophobic area, were used to predict the orientation of CCP-I relative to CCP-II. We tested this procedure successfully for factor H. For CD46, three clusters of structures differing in the tilt angle of the two domains were obtained. To test these models, we mutagenized the CCP modules. Four proteins, two without an oligosaccharide chain and two with mutated short amino acid segments, reached the cell surface efficiently. Only the protein without the CCP-I oligosaccharide chain maintained binding to the viral attachment protein hemagglutinin. These results are consistent with one of our models and suggest that the vital hemagglutinin does not bind at the membrane-distal tip of CD46, but near the concave CCP-I-II interface region.

KW - complement control protein module

KW - distance geometry

KW - FANTOM

KW - hemagglutinin binding

KW - hydrophobic solvent-accessible surface area

KW - measles virus receptor CD46

KW - module assembly

KW - Monte Carlo simulations

UR - http://www.scopus.com/inward/record.url?scp=0030935563&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030935563&partnerID=8YFLogxK

M3 - Article

VL - 6

SP - 588

EP - 597

JO - Protein Science

JF - Protein Science

SN - 0961-8368

IS - 3

ER -