A cluster of basic amino acids in the factor X serine protease mediates surface attachment of adenovirus/FX complexes

Margaret R Duffy; Angela C Bradshaw; Alan L Parker; John H McVey; Andrew H Baker

doi:10.1128/JVI.05382-11

A cluster of basic amino acids in the factor X serine protease mediates surface attachment of adenovirus/FX complexes

Margaret R Duffy, Angela C Bradshaw, Alan L Parker, John H McVey, Andrew H Baker

Research output: Contribution to journal › Article › peer-review

Abstract

Hepatocyte transduction following intravenous administration of adenovirus 5 (Ad5) is mediated by interaction between coagulation factor X (FX) and the hexon. The FX serine protease (SP) domain tethers the Ad5/FX complex to hepatocytes through binding heparan sulfate proteoglycans (HSPGs). Here, we identify the critical HSPG-interacting residues of FX. We generated an FX mutant by modifying seven residues in the SP domain. Surface plasmon resonance demonstrated that mutations did not affect binding to Ad5. FX-mediated, HSPG-associated cell binding and transduction were abolished. A cluster of basic amino acids in the SP domain therefore mediates surface interaction of the Ad/FX complex.

Original language	English
Pages (from-to)	10914-9
Number of pages	6
Journal	Journal of Virology
Volume	85
Issue number	20
DOIs	https://doi.org/10.1128/JVI.05382-11
Publication status	Published - Oct 2011

Keywords

Adenoviridae
Amino Acid Substitution
Amino Acids, Basic
Factor X
Heparan Sulfate Proteoglycans
Humans
Mutagenesis, Site-Directed
Mutant Proteins
Protein Binding
Surface Plasmon Resonance

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title = "A cluster of basic amino acids in the factor X serine protease mediates surface attachment of adenovirus/FX complexes",

abstract = "Hepatocyte transduction following intravenous administration of adenovirus 5 (Ad5) is mediated by interaction between coagulation factor X (FX) and the hexon. The FX serine protease (SP) domain tethers the Ad5/FX complex to hepatocytes through binding heparan sulfate proteoglycans (HSPGs). Here, we identify the critical HSPG-interacting residues of FX. We generated an FX mutant by modifying seven residues in the SP domain. Surface plasmon resonance demonstrated that mutations did not affect binding to Ad5. FX-mediated, HSPG-associated cell binding and transduction were abolished. A cluster of basic amino acids in the SP domain therefore mediates surface interaction of the Ad/FX complex.",

keywords = "Adenoviridae, Amino Acid Substitution, Amino Acids, Basic, Factor X, Heparan Sulfate Proteoglycans, Humans, Mutagenesis, Site-Directed, Mutant Proteins, Protein Binding, Surface Plasmon Resonance",

author = "Duffy, {Margaret R} and Bradshaw, {Angela C} and Parker, {Alan L} and McVey, {John H} and Baker, {Andrew H}",

year = "2011",

month = oct,

doi = "10.1128/JVI.05382-11",

language = "English",

volume = "85",

pages = "10914--9",

journal = "Journal of Virology",

issn = "0022-538X",

publisher = "American Society for Microbiology",

number = "20",

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TY - JOUR

T1 - A cluster of basic amino acids in the factor X serine protease mediates surface attachment of adenovirus/FX complexes

AU - Duffy, Margaret R

AU - Bradshaw, Angela C

AU - Parker, Alan L

AU - McVey, John H

AU - Baker, Andrew H

PY - 2011/10

Y1 - 2011/10

N2 - Hepatocyte transduction following intravenous administration of adenovirus 5 (Ad5) is mediated by interaction between coagulation factor X (FX) and the hexon. The FX serine protease (SP) domain tethers the Ad5/FX complex to hepatocytes through binding heparan sulfate proteoglycans (HSPGs). Here, we identify the critical HSPG-interacting residues of FX. We generated an FX mutant by modifying seven residues in the SP domain. Surface plasmon resonance demonstrated that mutations did not affect binding to Ad5. FX-mediated, HSPG-associated cell binding and transduction were abolished. A cluster of basic amino acids in the SP domain therefore mediates surface interaction of the Ad/FX complex.

AB - Hepatocyte transduction following intravenous administration of adenovirus 5 (Ad5) is mediated by interaction between coagulation factor X (FX) and the hexon. The FX serine protease (SP) domain tethers the Ad5/FX complex to hepatocytes through binding heparan sulfate proteoglycans (HSPGs). Here, we identify the critical HSPG-interacting residues of FX. We generated an FX mutant by modifying seven residues in the SP domain. Surface plasmon resonance demonstrated that mutations did not affect binding to Ad5. FX-mediated, HSPG-associated cell binding and transduction were abolished. A cluster of basic amino acids in the SP domain therefore mediates surface interaction of the Ad/FX complex.

KW - Adenoviridae

KW - Amino Acid Substitution

KW - Amino Acids, Basic

KW - Factor X

KW - Heparan Sulfate Proteoglycans

KW - Humans

KW - Mutagenesis, Site-Directed

KW - Mutant Proteins

KW - Protein Binding

KW - Surface Plasmon Resonance

U2 - 10.1128/JVI.05382-11

DO - 10.1128/JVI.05382-11

M3 - Article

C2 - 21849463

VL - 85

SP - 10914

EP - 10919

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 20

ER -

A cluster of basic amino acids in the factor X serine protease mediates surface attachment of adenovirus/FX complexes

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Keywords

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