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Internal dynamics of the homotrimeric HIV-1 viral coat protein gp41 on multiple time scales - PubMed

  • ️Tue Jan 01 2013

Internal dynamics of the homotrimeric HIV-1 viral coat protein gp41 on multiple time scales

Nils-Alexander Lakomek et al. Angew Chem Int Ed Engl. 2013.

No abstract available

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Figures

Figure 1
Figure 1

Schematic view of the studied gp411–194 construct, including the fusion peptide (FP), N-terminal heptad repeat (NHR), immuno-dominant loop region (IL), C-terminal heptad repeat (CHR), membrane proximal external region (MPER) and transmembrane helix (TM) anchoring gp41 to the viral envelope. The numbering 1–194 refers to the gp411–194 construct; the numbering 512–705 refers to the location in the Env precursor.

Figure 2
Figure 2

800 MHz 15N-1H TROSY-HSQC spectrum of 0.5 mM 2H,15N,13C gp411–194 in DPC micelles, 50mM sodium acetate, pH 4.0, 25 mM KCl, recorded at 40 °C.

Figure 3
Figure 3

15N relaxation data recorded for gp411–194 in DPC micelles: a) 15N R1 relaxation data recorded at 600 MHz (black) and 800 MHz (red) are highly consistent for both fields. b) R2,0 relaxation data (derived from R1> with a 2 kHz RF field; R1 contribution corrected), at 600 MHz (black) and 800 MHz. c) 15N-{1H} NOE values. d) Transverse CSA-dipolar cross-correlated relaxation rates ηxy. e) Hahn-echo transverse relaxation rates, R2β, at 600 MHz (black) and 800 MHz (red) for the slowly relaxing component of the 15N-{1H} doublets. Unlike the R1ρ experiment, all conformational exchange effects, R2ex, contribute to R2β and are not re-focused.

Figure 4
Figure 4

Homotrimeric gp41 shows a high degree of intrinsic mobility on the nanosecond and microsecond time scale. NMR and SAXS data are compatible with the pre-hairpin intermediate sampling a range of relative CHR vs NHR orientations (A), possibly in exchange with a low population of the late-fusion 6HB (C). A conformational change from the pre-hairpin intermediate to the late-fusion 6HB requires breaking up of the CHR three-helical bundle with concomitant disorder of the CHR and MPER region during the transition period (B). The large exchange broadening for CHR and MPER region is indicative of such a scenario. No NMR information on the relative arrangement of CHR, MPER and TM domains is available and the arrangement shown is purely schematic. Intense resonances observed for FP exclude a strong interaction between FP and TM, although weak PRE interactions point to their transient proximity.

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