Saturday, 26 May 2012

Lecture materials: Molecular architecture of native HIV-1 gp120 trimers by Jun Liu

FIGURE 4. Description of the conformational change in the gp120 trimer induced by CD4, Model for the conformational change from the unliganded (ac) to the CD4-bound state (bd) shown as top (ab) and front (cd) views. The gp120 core, CD4, V1/V2 and V3 stems are shown in white, yellow, red and green colours, respectively. e, Schematic description of the gp41 (blue) and gp120 (red/purple) regions of the trimeric spike and the conformational changes that occur upon CD4 binding. The yellow patch near the apex marks the location of the CD4 binding site in the unliganded spike and the green patch at the apex marks the location of the V3 loop region in the spike after CD4 binding. f, Schematic view of the consequence of the CD4-induced conformational changes for viral attachment to the target cell and interaction with chemokine receptors (green at top). Colours in f have same meaning as in e.

  • CD4 induces opening of trimer
  • CD4 binding contributes to entropy
  • Opening of trimer makes way for exposure of central gp 41 stalk.
  • The V3 loop region is released from the lateral edge of the apex of the spike to directly point towards the target cell
  • while the V1/V2 regions as well as the CD4 binding sites move away from the centre of the spike (Fig. 4b).
  • In native state, trimer is held together by strong contacts at gp 41 base and apex.
  • Little contact between other regions of neighbouring gp120 monomers
  • cause spike archituecture held together
  • sprung open on CD 4 binding
  • The outward movement of gp120 results in a steep change in the orientation of the two outermost domains (D1D2) of CD4 (Fig. 4e),
  • must draw the virus closer to the target cell membrane by virtue of the flexibility between the D1D2 and D3D4 domains of membrane-anchored CD4 (Fig. 4f). 

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