Concentration‐Dependent Structural Transition of the HIV‐1 gp41 MPER Peptide into α‐Helical Trimers
| Autor: | John M. Louis, Ad Bax, Sai Chaitanya Chiliveri |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Protein Conformation
alpha-Helical chemistry.chemical_classification Circular dichroism Aqueous solution 010405 organic chemistry Intermolecular force Trimer Peptide General Medicine General Chemistry Nuclear magnetic resonance spectroscopy 010402 general chemistry 01 natural sciences HIV Envelope Protein gp41 Article Catalysis 0104 chemical sciences Crystallography chemistry.chemical_compound Monomer chemistry Ionic strength HIV-1 Humans Peptides |
| Zdroj: | Angew Chem Int Ed Engl |
| ISSN: | 1521-3773 1433-7851 |
| DOI: | 10.1002/anie.202008804 |
| Popis: | 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 micro-molar 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. |
| Databáze: | OpenAIRE |
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