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Fully hydrophobic HIV gp41 adopts a hemifusion-like conformation in phospholipid bilayers
- Source :
- J Biol Chem
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- The HIV envelope glycoprotein mediates virus entry into target cells by fusing the virus lipid envelope with the cell membrane. This process requires large-scale conformational changes of the fusion protein gp41. Current understanding of the mechanisms with which gp41 induces membrane merger is limited by the fact that the hydrophobic N-terminal fusion peptide (FP) and C-terminal transmembrane domain (TMD) of the protein are challenging to characterize structurally in the lipid bilayer. Here we have expressed a gp41 construct that contains both termini, including the FP, the fusion peptide–proximal region (FPPR), the membrane-proximal external region (MPER), and the TMD. These hydrophobic domains are linked together by a shortened water-soluble ectodomain. We reconstituted this “short NC” gp41 into a virus-mimetic lipid membrane and conducted solid-state NMR experiments to probe the membrane-bound conformation and topology of the protein. (13)C chemical shifts indicate that the C-terminal MPER-TMD is predominantly α-helical, whereas the N-terminal FP-FPPR exhibits β-sheet character. Water and lipid (1)H polarization transfer to the protein revealed that the TMD is well-inserted into the lipid bilayer, whereas the FPPR and MPER are exposed to the membrane surface. Importantly, correlation signals between the FP-FPPR and the MPER are observed, providing evidence that the ectodomain is sufficiently collapsed to bring the N- and C-terminal hydrophobic domains into close proximity. These results support a hemifusion-like model of the short NC gp41 in which the ectodomain forms a partially folded hairpin that places the FPPR and MPER on the opposing surfaces of two lipid membranes.
- Subjects :
- Gene Expression Regulation, Viral
Models, Molecular
Protein Conformation, alpha-Helical
0301 basic medicine
Protein Conformation
Lipid Bilayers
Phospholipid
HIV Infections
Gp41
Biochemistry
Cell membrane
03 medical and health sciences
chemistry.chemical_compound
Protein Domains
medicine
Humans
Lipid bilayer
Molecular Biology
Phospholipids
030102 biochemistry & molecular biology
Chemistry
Cell Membrane
Water
Lipid bilayer fusion
Cell Biology
Virus Internalization
HIV Envelope Protein gp41
Transmembrane domain
030104 developmental biology
medicine.anatomical_structure
Ectodomain
Structural biology
Protein Structure and Folding
HIV-1
Biophysics
Protein Conformation, beta-Strand
Hydrophobic and Hydrophilic Interactions
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 294
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....e7d4396ca1f67db126ffd20e5eb41f7f