PMID- 22171273
OWN - NLM
STAT- MEDLINE
DCOM- 20120403
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 86
IP  - 5
DP  - 2012 Mar
TI  - The paramyxovirus fusion protein C-terminal region: mutagenesis indicates an 
      indivisible protein unit.
PG  - 2600-9
LID - 10.1128/JVI.06546-11 [doi]
AB  - Paramyxoviruses enter host cells by fusing the viral envelope with a host cell 
      membrane. Fusion is mediated by the viral fusion (F) protein, and it undergoes 
      large irreversible conformational changes to cause membrane merger. The C 
      terminus of PIV5 F contains a membrane-proximal 7-residue external region (MPER), 
      followed by the transmembrane (TM) domain and a 20-residue cytoplasmic tail. To 
      study the sequence requirements of the F protein C terminus for fusion, we 
      constructed chimeras containing the ectodomain of parainfluenza virus 5 F (PIV5 
      F) and either the MPER, the TM domain, or the cytoplasmic tail of the F proteins 
      of the paramyxoviruses measles virus, mumps virus, Newcastle disease virus, human 
      parainfluenza virus 3, and Nipah virus. The chimeras were expressed, and their 
      ability to cause cell fusion was analyzed. The chimeric proteins were variably 
      expressed at the cell surface. We found that chimeras containing the ectodomain 
      of PIV5 F with the C terminus of other paramyxoviruses were unable to cause cell 
      fusion. Fusion could be restored by decreasing the activation energy of refolding 
      through introduction of a destabilizing mutation (S443P). Replacing individual 
      regions, singly or doubly, in the chimeras with native PIV5 F sequences restored 
      fusion to various degrees, but it did not have an additive effect in restoring 
      activity. Thus, the F protein C terminus may be a specific structure that only 
      functions with its cognate ectodomain. Alanine scanning mutagenesis of MPER 
      indicates that it has a regulatory role in fusion since both hyperfusogenic and 
      hypofusogenic mutations were found.
FAU - Zokarkar, Aarohi
AU  - Zokarkar A
AD  - Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, 
      USA.
FAU - Lamb, Robert A
AU  - Lamb RA
LA  - eng
GR  - R01 AI023173/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - R01 AI-23173/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111214
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Viral Fusion Proteins)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Fusion
MH  - Cell Line
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Mutation
MH  - Paramyxoviridae Infections/veterinary/virology
MH  - Paramyxovirinae/*chemistry/*genetics/physiology
MH  - Rubulavirus/chemistry/*genetics/physiology
MH  - Sequence Alignment
MH  - Viral Fusion Proteins/*chemistry/*genetics/metabolism/physiology
PMC - PMC3302293
EDAT- 2011/12/16 06:00
MHDA- 2012/04/04 06:00
PMCR- 2012/09/01
CRDT- 2011/12/16 06:00
PHST- 2011/12/16 06:00 [entrez]
PHST- 2011/12/16 06:00 [pubmed]
PHST- 2012/04/04 06:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - JVI.06546-11 [pii]
AID - 06546-11 [pii]
AID - 10.1128/JVI.06546-11 [doi]
PST - ppublish
SO  - J Virol. 2012 Mar;86(5):2600-9. doi: 10.1128/JVI.06546-11. Epub 2011 Dec 14.