Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing

Willie Warren Craft; Rebecca Ellis Dutch

doi:10.1016/j.virol.2005.07.004

Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing

Willie Warren Craft, Rebecca Ellis Dutch

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

17 Scopus citations

Abstract

The Hendra virus fusion (HeV F) protein is synthesized as a precursor, F₀, and proteolytically cleaved into the mature F₁ and F₂ heterodimer, following an HDLVDGVK₁₀₉ motif. This cleavage event is required for fusogenic activity. To determine the amino acid requirements for processing of the HeV F protein, we constructed multiple mutants. Individual and simultaneous alanine substitutions of the eight residues immediately upstream of the cleavage site did not eliminate processing. A chimeric SV5 F protein in which the furin site was substituted for the VDGVK₁₀₉ motif of the HeV F protein was not processed but was expressed on the cell surface. Another chimeric SV5 F protein containing the HDLVDGVK₁₀₉ motif of the HeV F protein underwent partial cleavage. These data indicate that the upstream region can play a role in protease recognition, but is neither absolutely required nor sufficient for efficient processing of the HeV F protein.

Original language	English
Pages (from-to)	130-140
Number of pages	11
Journal	Virology
Volume	341
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2005.07.004
State	Published - Oct 10 2005

Bibliographical note

Funding Information:
This study was partially supported by the Ruth L. Kirschstein National Research Service Award (NIH) to WC and by NIH grants AI05157 and AI063052 to RED.

Keywords

Cleavage
Fusion protein
Hendra
Henipavirus
Paramyxovirus
Post-translational modifications

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2005.07.004

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title = "Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing",

abstract = "The Hendra virus fusion (HeV F) protein is synthesized as a precursor, F0, and proteolytically cleaved into the mature F1 and F2 heterodimer, following an HDLVDGVK109 motif. This cleavage event is required for fusogenic activity. To determine the amino acid requirements for processing of the HeV F protein, we constructed multiple mutants. Individual and simultaneous alanine substitutions of the eight residues immediately upstream of the cleavage site did not eliminate processing. A chimeric SV5 F protein in which the furin site was substituted for the VDGVK109 motif of the HeV F protein was not processed but was expressed on the cell surface. Another chimeric SV5 F protein containing the HDLVDGVK109 motif of the HeV F protein underwent partial cleavage. These data indicate that the upstream region can play a role in protease recognition, but is neither absolutely required nor sufficient for efficient processing of the HeV F protein.",

keywords = "Cleavage, Fusion protein, Hendra, Henipavirus, Paramyxovirus, Post-translational modifications",

author = "Craft, {Willie Warren} and Dutch, {Rebecca Ellis}",

note = "Funding Information: This study was partially supported by the Ruth L. Kirschstein National Research Service Award (NIH) to WC and by NIH grants AI05157 and AI063052 to RED.",

year = "2005",

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doi = "10.1016/j.virol.2005.07.004",

language = "English",

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T1 - Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing

AU - Craft, Willie Warren

AU - Dutch, Rebecca Ellis

N1 - Funding Information: This study was partially supported by the Ruth L. Kirschstein National Research Service Award (NIH) to WC and by NIH grants AI05157 and AI063052 to RED.

PY - 2005/10/10

Y1 - 2005/10/10

N2 - The Hendra virus fusion (HeV F) protein is synthesized as a precursor, F0, and proteolytically cleaved into the mature F1 and F2 heterodimer, following an HDLVDGVK109 motif. This cleavage event is required for fusogenic activity. To determine the amino acid requirements for processing of the HeV F protein, we constructed multiple mutants. Individual and simultaneous alanine substitutions of the eight residues immediately upstream of the cleavage site did not eliminate processing. A chimeric SV5 F protein in which the furin site was substituted for the VDGVK109 motif of the HeV F protein was not processed but was expressed on the cell surface. Another chimeric SV5 F protein containing the HDLVDGVK109 motif of the HeV F protein underwent partial cleavage. These data indicate that the upstream region can play a role in protease recognition, but is neither absolutely required nor sufficient for efficient processing of the HeV F protein.

AB - The Hendra virus fusion (HeV F) protein is synthesized as a precursor, F0, and proteolytically cleaved into the mature F1 and F2 heterodimer, following an HDLVDGVK109 motif. This cleavage event is required for fusogenic activity. To determine the amino acid requirements for processing of the HeV F protein, we constructed multiple mutants. Individual and simultaneous alanine substitutions of the eight residues immediately upstream of the cleavage site did not eliminate processing. A chimeric SV5 F protein in which the furin site was substituted for the VDGVK109 motif of the HeV F protein was not processed but was expressed on the cell surface. Another chimeric SV5 F protein containing the HDLVDGVK109 motif of the HeV F protein underwent partial cleavage. These data indicate that the upstream region can play a role in protease recognition, but is neither absolutely required nor sufficient for efficient processing of the HeV F protein.

KW - Cleavage

KW - Fusion protein

KW - Hendra

KW - Henipavirus

KW - Paramyxovirus

KW - Post-translational modifications

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DO - 10.1016/j.virol.2005.07.004

M3 - Article

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AN - SCOPUS:25444472562

SN - 0042-6822

VL - 341

SP - 130

EP - 140

JO - Virology

JF - Virology

IS - 1

ER -

Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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