Tilted, Uninterrupted, Monomeric HIV-1 gp41 Transmembrane Helix from Residual Dipolar Couplings.
Sai Chaitanya ChiliveriJohn M LouisRodolfo GhirlandoJames L BaberAdriaan BaxPublished in: Journal of the American Chemical Society (2017)
Cryo-electron microscopy and X-ray crystallography have shown that the pre- and postfusion states of the HIV-1 gp41 viral coat protein, although very different from one another, each adopt C3 symmetric structures. A stable homotrimeric structure for the transmembrane domain (TM) also was modeled and supported by experimental data. For a C3 symmetric structure, alignment in an anisotropic medium must be axially symmetric, with the unique axis of the alignment tensor coinciding with the C3 axis. However, NMR residual dipolar couplings (RDCs) measured under three different alignment conditions were found to be incompatible with C3 symmetry. Subsequent measurements by paramagnetic relaxation enhancement, analytical ultracentrifugation, and DEER EPR, indicate that the transmembrane domain is monomeric. 15N NMR relaxation data and RDCs show that TM is highly ordered and uninterrupted for a total length of 32 residues, extending well into the membrane proximal external region.
Keyphrases
- electron microscopy
- high resolution
- antiretroviral therapy
- hiv positive
- hiv testing
- hiv infected
- human immunodeficiency virus
- hepatitis c virus
- electronic health record
- magnetic resonance
- men who have sex with men
- hiv aids
- big data
- solid state
- single molecule
- mass spectrometry
- south africa
- sars cov
- direct oral anticoagulants
- catheter ablation
- magnetic resonance imaging
- atrial fibrillation
- liquid chromatography
- machine learning
- dna binding
- protein protein
- transcription factor
- contrast enhanced