Solution structure of the Equine Infectious Anemia Virus p9 protein: a rationalization of its different ALIX binding requirements compared to the analogous HIV-p6 protein

2.50
Hdl Handle:
http://hdl.handle.net/10033/620696
Title:
Solution structure of the Equine Infectious Anemia Virus p9 protein: a rationalization of its different ALIX binding requirements compared to the analogous HIV-p6 protein
Authors:
Sharma, Alok; Bruns, Karsten; Röder, René; Henklein, Peter; Votteler, Jörg; Wray, Victor; Schubert, Ulrich
Abstract:
Abstract Background The equine infection anemia virus (EIAV) p9 Gag protein contains the late (L-) domain required for efficient virus release of nascent virions from the cell membrane of infected cell. Results In the present study the p9 protein and N- and C-terminal fragments (residues 1-21 and 22-51, respectively) were chemically synthesized and used for structural analyses. Circular dichroism and 1H-NMR spectroscopy provide the first molecular insight into the secondary structure and folding of this 51-amino acid protein under different solution conditions. Qualitative 1H-chemical shift and NOE data indicate that in a pure aqueous environment p9 favors an unstructured state. In its most structured state under hydrophobic conditions, p9 adopts a stable helical structure within the C-terminus. Quantitative NOE data further revealed that this α-helix extends from Ser-27 to Ser-48, while the N-terminal residues remain unstructured. The structural elements identified for p9 differ substantially from that of the functional homologous HIV-1 p6 protein. Conclusions These structural differences are discussed in the context of the different types of L-domains regulating distinct cellular pathways in virus budding. EIAV p9 mediates virus release by recruiting the ALG2-interacting protein X (ALIX) via the YPDL-motif to the site of virus budding, the counterpart of the YPXnL-motif found in p6. However, p6 contains an additional PTAP L-domain that promotes HIV-1 release by binding to the tumor susceptibility gene 101 (Tsg101). The notion that structures found in p9 differ form that of p6 further support the idea that different mechanisms regulate binding of ALIX to primary versus secondary L-domains types.
Citation:
BMC Structural Biology. 2009 Dec 17;9(1):74
Issue Date:
17-Dec-2009
URI:
http://dx.doi.org/10.1186/1472-6807-9-74; http://hdl.handle.net/10033/620696
Type:
Journal Article
Appears in Collections:
Publications from RG Biophysical Analysis (BA)

Full metadata record

DC FieldValue Language
dc.contributor.authorSharma, Aloken
dc.contributor.authorBruns, Karstenen
dc.contributor.authorRöder, Renéen
dc.contributor.authorHenklein, Peteren
dc.contributor.authorVotteler, Jörgen
dc.contributor.authorWray, Victoren
dc.contributor.authorSchubert, Ulrichen
dc.date.accessioned2017-01-13T09:49:46Z-
dc.date.available2017-01-13T09:49:46Z-
dc.date.issued2009-12-17en
dc.identifier.citationBMC Structural Biology. 2009 Dec 17;9(1):74en
dc.identifier.urihttp://dx.doi.org/10.1186/1472-6807-9-74en
dc.identifier.urihttp://hdl.handle.net/10033/620696-
dc.description.abstractAbstract Background The equine infection anemia virus (EIAV) p9 Gag protein contains the late (L-) domain required for efficient virus release of nascent virions from the cell membrane of infected cell. Results In the present study the p9 protein and N- and C-terminal fragments (residues 1-21 and 22-51, respectively) were chemically synthesized and used for structural analyses. Circular dichroism and 1H-NMR spectroscopy provide the first molecular insight into the secondary structure and folding of this 51-amino acid protein under different solution conditions. Qualitative 1H-chemical shift and NOE data indicate that in a pure aqueous environment p9 favors an unstructured state. In its most structured state under hydrophobic conditions, p9 adopts a stable helical structure within the C-terminus. Quantitative NOE data further revealed that this α-helix extends from Ser-27 to Ser-48, while the N-terminal residues remain unstructured. The structural elements identified for p9 differ substantially from that of the functional homologous HIV-1 p6 protein. Conclusions These structural differences are discussed in the context of the different types of L-domains regulating distinct cellular pathways in virus budding. EIAV p9 mediates virus release by recruiting the ALG2-interacting protein X (ALIX) via the YPDL-motif to the site of virus budding, the counterpart of the YPXnL-motif found in p6. However, p6 contains an additional PTAP L-domain that promotes HIV-1 release by binding to the tumor susceptibility gene 101 (Tsg101). The notion that structures found in p9 differ form that of p6 further support the idea that different mechanisms regulate binding of ALIX to primary versus secondary L-domains types.en
dc.titleSolution structure of the Equine Infectious Anemia Virus p9 protein: a rationalization of its different ALIX binding requirements compared to the analogous HIV-p6 proteinen
dc.typeJournal Articleen
dc.language.rfc3066enen
dc.rights.holderSharma et al.en
dc.date.updated2015-09-04T08:31:10Zen
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