2RLJ

NMR Structure of Ebola fusion peptide in SDS micelles at pH 7

Summary for 2RLJ

• Entry DOI: 10.2210/pdb2rlj/pdb
• NMR Information: BMRB: 11004
• Descriptor: Envelope glycoprotein (1 entity in total)
• Functional Keywords: fusion peptide, sds micelles, ebola virus, filovirus, viral protein
• Biological source: Zaire ebolavirus
• Cellular location: GP2: Virion membrane; Single-pass type I membrane protein. GP1: Virion membrane; Peripheral membrane protein. GP2-delta: Secreted: Q05320
• Total number of polymer chains: 1
• Total formula weight: 1574.82

Authors

Freitas, M.S.,Gaspar, L.P.,Lorenzoni, M.,Almeida, F.C.,Tinoco, L.W.,Almeida, M.S.,Maia, L.F.,Degreve, L.,Valente, A.P.,Silva, J.L. (deposition date: 2007-07-05, release date: 2007-08-07, Last modification date: 2024-05-29)

Primary citation

Freitas, M.S.,Gaspar, L.P.,Lorenzoni, M.,Almeida, F.C.,Tinoco, L.W.,Almeida, M.S.,Maia, L.F.,Degreve, L.,Valente, A.P.,Silva, J.L.
Structure of the Ebola fusion peptide in a membrane-mimetic environment and the interaction with lipid rafts.
J.Biol.Chem., 282:27306-27314, 2007

PubMed Abstract: The fusion peptide EBO(16) (GAAIGLAWIPYFGPAA) comprises the fusion domain of an internal sequence located in the envelope fusion glycoprotein (GP2) of the Ebola virus. This region interacts with the cellular membrane of the host and leads to membrane fusion. To gain insight into the mechanism of the peptide-membrane interaction and fusion, insertion of the peptide was modeled by experiments in which the tryptophan fluorescence and (1)H NMR were monitored in the presence of sodium dodecyl sulfate micelles or in the presence of detergent-resistant membrane fractions. In the presence of SDS micelles, EBO(16) undergoes a random coil-helix transition, showing a tendency to self-associate. The three-dimensional structure displays a 3(10)-helix in the central part of molecule, similar to the fusion peptides of many known membrane fusion proteins. Our results also reveal that EBO(16) can interact with detergent-resistant membrane fractions and strongly suggest that Trp-8 and Phe-12 are important for structure maintenance within the membrane bilayer. Replacement of tryptophan 8 with alanine (W8A) resulted in dramatic loss of helical structure, proving the importance of the aromatic ring in stabilizing the helix. Molecular dynamics studies of the interaction between the peptide and the target membrane also corroborated the crucial participation of these aromatic residues. The aromatic-aromatic interaction may provide a mechanism for the free energy coupling between random coil-helical transition and membrane anchoring. Our data shed light on the structural "domains" of fusion peptides and provide a clue for the development of a drug that might block the early steps of viral infection.

PubMed: 17545161
DOI: 10.1074/jbc.M611864200

Experimental method

SOLUTION NMR