Irreversible unfolding of the neutral pH form of influenza hemagglutinin demonstrates that it is not in a metastable state.


Abstract

The thermal denaturation of the proteins of influenza virus has been measured by differential scanning calorimetry in the presence and absence of lipids as a function of scan rate. We have applied theories of irreversible thermodynamics to obtain the activation energy. In the presence of liposomes of dioleoylphosphatidylcholine with the ganglioside, GD(1a), the denaturation temperature of the hemagglutinin protein is lowered. This lowering of thermal stability is also reflected in the temperature dependence of the circular dichroism spectra. Quasi-elastic light scattering confirms that liposomes containing GD(1a) interact with the virus and inhibit the growth in the size of the particle as a function of temperature. Although the virus can fuse with the liposomes at higher temperatures, the enthalpy change for this process is not detectable. Our results also demonstrate that the compact folded structure of the influenza hemagglutinin protein is not a kinetically trapped metastable high-energy form. Study holds ProTherm entries: 16206, 16207, 16208, 16209, 16210, 16211, 16212, 16213, 16214, 16215, 16216, 16217, 16218, 16219, 16220, 16221, 16222, 16223, 16224, 16225, 16226, 16227, 16228, 16229 Extra Details: influenza virus; lipids; temperature dependence; enthalpy change

Submission Details

ID: 5aEA97hM

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:47 p.m.

Version: 1

Publication Details
Epand RF;Epand RM,Biochemistry (2003) Irreversible unfolding of the neutral pH form of influenza hemagglutinin demonstrates that it is not in a metastable state. PMID:12718548
Additional Information

Study Summary

Number of data points 48
Proteins Hemagglutinin ; Hemagglutinin
Unique complexes 1
Assays/Quantities/Protocols Experimental Assay: dHcal pH:6.0 ; Experimental Assay: Tm pH:6.0 ; Experimental Assay: dHcal pH:7.4 ; Experimental Assay: Tm pH:7.4
Libraries Mutations for sequence A:QDLPGNDNSTATLCLGHHAVPNGTLVKTITDDQIEVTNATELVQSSSTGKICNNPHRILDGIDCTLIDALLGDPHCDVFQNETWDLFVERSKAFSNCYPYDVPDYASLRSLVASSGTLEFITEGFTWTGVTQNGGSNACKRGPGSGFFSRLNWLTKSGSTYPVLNVTMPNNDNFDKLYIWGIHHPSTNQEQTSLYVQASGRVTVSTRRSQQTIIPNIGSRPWVRGLSSRISIYWTIVKPGDVLVINSNGNLIAPRGYFKMRTGKSSIMRSDAPIDTCISECITPNGSIPNDKPFQNVNKITYGACPKYVKQNTLKLATGMRNVPEKQT/B:GLFGAIAGFIENGWEGMIDGWYGFRHQNSEGTGQAADLKSTQAAIDQINGKLNRVIEKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEMNKLFEKTRRQLRENAEEMGNGCFKIYHKCDNACIESIRNGTYDHDVYRDEALNNRFQIKG/C:QDLPGNDNSTATLCLGHHAVPNGTLVKTITDDQIEVTNATELVQSSSTGKICNNPHRILDGIDCTLIDALLGDPHCDVFQNETWDLFVERSKAFSNCYPYDVPDYASLRSLVASSGTLEFITEGFTWTGVTQNGGSNACKRGPGSGFFSRLNWLTKSGSTYPVLNVTMPNNDNFDKLYIWGIHHPSTNQEQTSLYVQASGRVTVSTRRSQQTIIPNIGSRPWVRGLSSRISIYWTIVKPGDVLVINSNGNLIAPRGYFKMRTGKSSIMRSDAPIDTCISECITPNGSIPNDKPFQNVNKITYGACPKYVKQNTLKLATGMRNVPEKQT/D:GLFGAIAGFIENGWEGMIDGWYGFRHQNSEGTGQAADLKSTQAAIDQINGKLNRVIEKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEMNKLFEKTRRQLRENAEEMGNGCFKIYHKCDNACIESIRNGTYDHDVYRDEALNNRFQIKG/E:QDLPGNDNSTATLCLGHHAVPNGTLVKTITDDQIEVTNATELVQSSSTGKICNNPHRILDGIDCTLIDALLGDPHCDVFQNETWDLFVERSKAFSNCYPYDVPDYASLRSLVASSGTLEFITEGFTWTGVTQNGGSNACKRGPGSGFFSRLNWLTKSGSTYPVLNVTMPNNDNFDKLYIWGIHHPSTNQEQTSLYVQASGRVTVSTRRSQQTIIPNIGSRPWVRGLSSRISIYWTIVKPGDVLVINSNGNLIAPRGYFKMRTGKSSIMRSDAPIDTCISECITPNGSIPNDKPFQNVNKITYGACPKYVKQNTLKLATGMRNVPEKQT/F:GLFGAIAGFIENGWEGMIDGWYGFRHQNSEGTGQAADLKSTQAAIDQINGKLNRVIEKTNEKFHQIEKEFSEVEGRIQDLEKYVEDTKIDLWSYNAELLVALENQHTIDLTDSEMNKLFEKTRRQLRENAEEMGNGCFKIYHKCDNACIESIRNGTYDHDVYRDEALNNRFQIKG

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
600.0 A,B,C,D,E,F Hemagglutinin P03437 HEMA_I68A0
597.3 A,B,C,D,E,F Hemagglutinin Q91MA7 HEMA_I68A4
594.6 A,B,C,D,E,F Hemagglutinin P03436 HEMA_I68A6
594.6 A,B,C,D,E,F Hemagglutinin P03438 HEMA_I000X
593.6999999999999 A,B,C,D,E,F Hemagglutinin P03449 HEMA_I71A1
586.5 A,B,C,D,E,F Hemagglutinin P12583 HEMA_I80A6
586.5 A,B,C,D,E,F Hemagglutinin P19106 HEMA_I72A2
586.5 A,B,C,D,E,F Hemagglutinin P03439 HEMA_I72A3
586.5 A,B,C,D,E,F Hemagglutinin Q2ICR0 HEMA_I72A4
582.0 A,B,C,D,E,F Hemagglutinin Q1PUD9 HEMA_I73A5
581.1 A,B,C,D,E,F Hemagglutinin P03442 HEMA_I63A3
577.5 A,B,C,D,E,F Hemagglutinin P26134 HEMA_I76A3
582.3000000000001 A,B,C,D,E,F Hemagglutinin P12585 HEMA_I82A5
581.7 A,B,C,D,E,F Hemagglutinin P12588 HEMA_I85A2
582.3000000000001 A,B,C,D,E,F Hemagglutinin P12584 HEMA_I80A7
572.1 A,B,C,D,E,F Hemagglutinin P26138 HEMA_I78A4
574.8 A,B,C,D,E,F Hemagglutinin P03435 HEMA_I75A3
572.1 A,B,C,D,E,F Hemagglutinin Q2RFA5 HEMA_I76A6
563.4 A,B,C,D,E,F Hemagglutinin Q30NQ1 HEMA_I75A0
571.2 A,B,C,D,E,F Hemagglutinin P26139 HEMA_I77A4
578.4 A,B,C,D,E,F Hemagglutinin P11134 HEMA_I82A4
579.6 A,B,C,D,E,F Hemagglutinin P12587 HEMA_I85A1
576.0 A,B,C,D,E,F Hemagglutinin P43257 HEMA_I75A2
571.5 A,B,C,D,E,F Hemagglutinin P26135 HEMA_I74A2
576.9000000000001 A,B,C,D,E,F Hemagglutinin P12582 HEMA_I77A6
578.4 A,B,C,D,E,F Hemagglutinin P43258 HEMA_I76AD
570.9 A,B,C,D,E,F Hemagglutinin P43260 HEMA_I76AC
571.5 A,B,C,D,E,F Hemagglutinin P11133 HEMA_I78A9
271.5 A,C,E Hemagglutinin P26141 HEMA_I84A5
569.4 A,B,C,D,E,F Hemagglutinin Q2VND2 HEMA_I78A8
568.5 A,B,C,D,E,F Hemagglutinin P03440 HEMA_I77A8
569.4 A,B,C,D,E,F Hemagglutinin Q2VNF2 HEMA_I78A7
575.1 A,B,C,D,E,F Hemagglutinin P43259 HEMA_I77A7
573.0 A,B,C,D,E,F Hemagglutinin P12586 HEMA_I82A6
554.4 A,B,C,D,E,F Hemagglutinin Q03909 HEMA_I89A7
293.1 B,D,F Hemagglutinin Q2RCH5 HEMA_I80A4
284.70000000000005 B,D,F Hemagglutinin Q38SQ8 HEMA_I83A8
291.29999999999995 B,D,F Hemagglutinin P03441 HEMA_I79A0
289.79999999999995 B,D,F Hemagglutinin P12589 HEMA_I86A1
279.29999999999995 B,D,F Hemagglutinin P15658 HEMA_I63A2
295.5 A,C,E Hemagglutinin P04664 HEMA_I69A0
295.5 A,C,E Hemagglutinin P04663 HEMA_I70A0
288.0 B,D,F Hemagglutinin P17002 HEMA_I63A4
284.4 B,D,F Hemagglutinin P16994 HEMA_I72A0
282.9 B,D,F Hemagglutinin P17000 HEMA_I71A3
279.29999999999995 B,D,F Hemagglutinin P16995 HEMA_I76A8
277.79999999999995 B,D,F Hemagglutinin P16998 HEMA_I80AB
277.79999999999995 B,D,F Hemagglutinin Q82559 HEMA_I81A2
277.79999999999995 B,D,F Hemagglutinin Q08011 HEMA_I89A8
284.70000000000005 B,D,F Hemagglutinin O11283 HEMA_I89A2
270.9 B,D,F Hemagglutinin P16997 HEMA_I76AJ
270.9 B,D,F Hemagglutinin P19699 HEMA_I86A2
270.9 B,D,F Hemagglutinin P17001 HEMA_I86A3