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Concentration‐Dependent Structural Transition of the HIV‐1 gp41 MPER Peptide into α‐Helical Trimers
Author(s) -
Chiliveri Sai Chaitanya,
Louis John M.,
Bax Ad
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202008804
Subject(s) - trimer , chemistry , monomer , crystallography , circular dichroism , gp41 , hydrogen bond , folding (dsp implementation) , intermolecular force , molecule , dimer , epitope , polymer , organic chemistry , antibody , electrical engineering , immunology , biology , engineering
The membrane proximal external region (MPER) of HIV‐1 gp41 contains epitopes for at least four broadly neutralizing antibodies. Depending on solution conditions and construct design, different structures have been reported for this segment. We show that in aqueous solution the MPER fragment (gp160 660–674 ) exists in a monomer‐trimer equilibrium with an association constant in the micromolar range. Thermodynamic analysis reveals that the association is exothermic, more favorable in D 2 O than H 2 O, and increases with ionic strength, indicating hydrophobically driven intermolecular interactions. Circular dichroism, 13 C α chemical shifts, NOE, and hydrogen exchange rates reveal that MPER undergoes a structural transition from predominately unfolded monomer at low concentrations to an α‐helical trimer at high concentrations. This result has implications for antibody recognition of MPER prior to and during the process where gp41 switches from a pre‐hairpin intermediate to its post‐fusion 6‐helical bundle state.