Supplementary Materials

Structural and mechanistic bases for a potent HIV-1 capsid inhibitor

Stephanie M. Bester, Guochao Wei, Haiyan Zhao, Daniel Adu-Ampratwum, Naseer Iqbal, Valentine V. Courouble, Ashwanth C. Francis, Arun S. Annamalai, Parmit K. Singh, Nikoloz Shkriabai, Peter Van Blerkom, James Morrison, Eric M. Poeschla, Alan N. Engelman, Gregory B. Melikyan, Patrick R. Griffin, James R. Fuchs, Francisco J. Asturias*, Mamuka Kvaratskhelia

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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  • Materials and Methods
  • Figs. S1 to S53
  • Tables S1 to S5
  • Captions for Movies S1 to S10
  • 1H, 13C, and HSQC NMR spectra of GS-6207 and synthetic intermediates
  • References
MDAR Reproducibility Checklist

Images, Video, and Other Media

Movie S1
Side view of conformational morph of CA hexamer structures derived from cryo-EM of CA tubes transitioning from GS-6207 bound A92E CA hexamer (PDB ID: 6VWS) to unliganded A92E CA hexamer (PDB ID: 3J34). The conformational morphing was achieved through Chimera (47) by superimposing respective hexamers. It is particularly noticeable in the bottom right how the gold CTD moves away from the gray NTD in the absence of the inhibitor in the unliganded A92E CA hexamer structure (PDB ID: 3J34).
Movie S2
Top view of movie S1 showing conformational morph of CA hexamer structures derived from cryo-EM of CA tubes transitioning from GS-6207 bound A92E CA hexamer (PDB ID: 6VWS) to unliganded A92E CA hexamer (PDB ID: 3J34).
Movie S3
Side view of conformational morph of CA hexamers transitioning from GS-6207 bound CA hexamer derived from our cryo-EM of CA tubes + GS-6207 (PDB ID: 6VWS) to the CA hexamer structure derived from cryo-ET of native HIV-1 particles (PDB ID: 5MCX). The conformational morphing was achieved through Chimera (47) by superimposing respective hexamers. It is particularly noticeable in the bottom right how the gold CTD moves away from the gray NTD in the absence of the inhibitor in the native CA shell of HIV-1 particles (PDB ID: 5MCX).
Movie S4
Top view of movie S3 showing conformational morph of CA hexamers transitioning from GS-6207 bound CA hexamer derived from our cryo-EM of CA tubes + GS-6207 (PDB ID: 6VWS) to CA hexamer structure derived from cryo-ET of native HIV-1 particles (PDB ID: 5MCX).
Movie S5
Side view of conformational morph of CA hexamers transitioning from a flat surface seen in the crystal structure (PDB ID: 6VKV) to the curved topology seen in our cryo-EM structure 106 of CA tubes + GS-6207 (PDB ID: 6VWS). The conformational morphing was achieved through Chimera (58) by superimposing respective hexamers. It is particularly noticeable in the bottom right how gold CTD remains closely associated with gray NTD in the presence of GS-6207 as CA hexamer changes its conformation from a flat (PDB ID: 6VKV) to the curved (PDB ID: 6VWS) surface. GS-6207 is not shown because the program allows morphing of only proteins but not the inhibitor.
Movie S6
Top view of movie S5 showing conformational morph of CA hexamers transitioning from a flat surface seen in the crystal structure (PDB ID: 6VKV) to the curved topology seen in our cryo-EM structure of CA tubes + GS-6207 (PDB ID: 6VWS).
Movie S7
Side view of conformational morph of CA hexamers transitioning from a flat surface seen in the crystal structure (PDB ID: 6VKV) to the curved topology seen in the cryo-EM structure of unliganded CA tubes (PDB ID: 3J34). The conformational morphing was achieved through Chimera (58) by superimposing respective hexamers. It is particularly noticeable in the bottom right how gold CTD moves away from gray NTD in the absence of the inhibitor as CA hexamer changes its conformation from a flat (PDB ID: 6VKV) to the curved (PDB ID: 3J34) surface.
Movie S8
Top view of movie S7 showing conformational morph of CA hexamers transitioning from a flat surface seen in the crystal structure (PDB ID: 6VKV) to the curved topology seen in the cryo-EM structure of unliganded tube (PDB ID: 3J34).
Movie S9
Side view of conformational morph of CA hexamers transitioning from a flat surface seen in the crystal structure (PDB ID: 6VKV) to the curved topology seen in the cryo-ET structure of native HIV-1 particles (PDB ID: 5MCX). The conformational morphing was achieved through Chimera (58) by superimposing respective hexamers. It is particularly noticeable in the bottom right how gold CTD moves away from gray NTD in the absence of the inhibitor as CA 107 hexamer changes its conformation from a flat (PDB ID: 6VKV) surface to the curved topology (PDB ID: 5MCX) of the native CA shell of HIV-1 particles.
Movie S10
Top view of movie S9 showing conformational morph of CA hexamers transitioning from a flat surface seen in the crystal structure (PDB ID: 6VKV) to the curved topology seen in the cryo-ET structure of native HIV-1 particles (PDB ID: 5MCX).