Immobilization of the N-terminal helix stabilizes prefusion paramyxovirus fusion proteins
被引:4
作者:
Song, Albert S.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USANorthwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
Song, Albert S.
[1
]
Poor, Taylor A.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USANorthwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
Poor, Taylor A.
[1
]
Abriata, Luciano A.
论文数: 0引用数: 0
h-index: 0
机构:
Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1050 Lausanne, Switzerland
Swiss Inst Bioinformat, CH-1015 Lausanne, SwitzerlandNorthwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
Abriata, Luciano A.
[2
,3
]
Jardetzky, Theodore S.
论文数: 0引用数: 0
h-index: 0
机构:
Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USANorthwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
Jardetzky, Theodore S.
[4
]
Dal Peraro, Matteo
论文数: 0引用数: 0
h-index: 0
机构:
Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1050 Lausanne, Switzerland
Swiss Inst Bioinformat, CH-1015 Lausanne, SwitzerlandNorthwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
Dal Peraro, Matteo
[2
,3
]
Lamb, Robert A.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL 60208 USANorthwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
Lamb, Robert A.
[1
,5
]
机构:
[1] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
Parainfluenza virus 5 (PIV5) is an enveloped, single-stranded, negative-sense RNA virus of the Paramyxoviridae family. PIV5 fusion and entry are mediated by the coordinated action of the receptor-binding protein, hemagglutinin-neuraminidase (HN), and the fusion protein (F). Upon triggering by HN, F undergoes an irreversible ATP-and pH-independent conformational change, going down an energy gradient from a metastable prefusion state to a highly stable postfusion state. Previous studies have highlighted key conformational changes in the F-protein refolding pathway, but a detailed understanding of prefusion F-protein metastability remains elusive. Here, using two previously described F-protein mutations (S443D or P22L), we examine the capacity tomodulate PIV5 F stability and the mechanisms by which these point mutants act. The S443D mutation destabilizes prefusion F proteins by disrupting a hydrogen bond network at the base of the F-protein globular head. The introduction of a P22L mutation robustly rescues destabilized F proteins through a local hydrophobic interaction between the N-terminal helix and a hydrophobic pocket. Prefusion stabilization conferred by a P22L-homologous mutation is demonstrated in the F protein of Newcastle disease virus, a paramyxovirus of a different genus, suggesting a conserved stabilizing structural element within the paramyxovirus family. Taken together, the available data suggest that movement of the N-terminal helix is a necessary early step for paramyxovirus F-protein refolding and presents a novel target for structure-based drug design.
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Stewart-Jones, Guillaume B. E.
Thomas, Paul V.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Thomas, Paul V.
Chen, Man
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Chen, Man
Druz, Aliaksandr
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Druz, Aliaksandr
Joyce, M. Gordon
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Joyce, M. Gordon
Kong, Wing-Pui
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Kong, Wing-Pui
Sastry, Mallika
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Sastry, Mallika
Soto, Cinque
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Soto, Cinque
Yang, Yongping
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Yang, Yongping
Zhang, Baoshan
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Zhang, Baoshan
Chen, Lei
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Chen, Lei
Chuang, Gwo-Yu
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Chuang, Gwo-Yu
Georgiev, Ivelin S.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Georgiev, Ivelin S.
McLellan, Jason S.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
McLellan, Jason S.
Srivatsan, Sanjay
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Srivatsan, Sanjay
Zhou, Tongqing
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Zhou, Tongqing
Baxa, Ulrich
论文数: 0引用数: 0
h-index: 0
机构:
Leidos Biomed Res Inc, Electron Microscopy Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Baxa, Ulrich
Mascola, John R.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Mascola, John R.
Graham, Barney S.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Graham, Barney S.
Kwong, Peter D.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Welch, Brett D.
Paduch, Marcin
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Paduch, Marcin
Leser, George P.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Leser, George P.
Bergman, Zachary
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Bergman, Zachary
Kors, Christopher A.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Kors, Christopher A.
Paterson, Reay G.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Paterson, Reay G.
Jardetzky, Theodore S.
论文数: 0引用数: 0
h-index: 0
机构:
Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Jardetzky, Theodore S.
Kossiakoff, Anthony A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Kossiakoff, Anthony A.
Lamb, Robert A.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Stewart-Jones, Guillaume B. E.
Thomas, Paul V.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Thomas, Paul V.
Chen, Man
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Chen, Man
Druz, Aliaksandr
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Druz, Aliaksandr
Joyce, M. Gordon
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Joyce, M. Gordon
Kong, Wing-Pui
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Kong, Wing-Pui
Sastry, Mallika
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Sastry, Mallika
Soto, Cinque
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Soto, Cinque
Yang, Yongping
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Yang, Yongping
Zhang, Baoshan
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Zhang, Baoshan
Chen, Lei
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Chen, Lei
Chuang, Gwo-Yu
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Chuang, Gwo-Yu
Georgiev, Ivelin S.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Georgiev, Ivelin S.
McLellan, Jason S.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
McLellan, Jason S.
Srivatsan, Sanjay
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Srivatsan, Sanjay
Zhou, Tongqing
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Zhou, Tongqing
Baxa, Ulrich
论文数: 0引用数: 0
h-index: 0
机构:
Leidos Biomed Res Inc, Electron Microscopy Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Baxa, Ulrich
Mascola, John R.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Mascola, John R.
Graham, Barney S.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
Graham, Barney S.
Kwong, Peter D.
论文数: 0引用数: 0
h-index: 0
机构:
NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USANIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Welch, Brett D.
Paduch, Marcin
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Paduch, Marcin
Leser, George P.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Leser, George P.
Bergman, Zachary
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Bergman, Zachary
Kors, Christopher A.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Kors, Christopher A.
Paterson, Reay G.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Paterson, Reay G.
Jardetzky, Theodore S.
论文数: 0引用数: 0
h-index: 0
机构:
Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Jardetzky, Theodore S.
Kossiakoff, Anthony A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA
Kossiakoff, Anthony A.
Lamb, Robert A.
论文数: 0引用数: 0
h-index: 0
机构:
Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
Northwestern Univ, Howard Hughes Med Inst, Evanston, IL USANorthwestern Univ, Dept Mol Biosci, Evanston, IL USA