The Proline-rich regions of human ALIX, human TSG101, and Saccharomyces cerevisiae Vps23. Pro residues are highlighted in blue background. PRMs with identified functions are boxed. The arrows points to their binding partners as annotated on the figure.

The domain organization of ALIX is depicted schematically and colored separately: Bro1 domain (light brown), V domain (blue (Arm1), green (Arm2)) and PRR region (purple). The PRR tail autoinhibits ALIX, shown in a putative closed conformation (left panel) (32, 33). ALIX appears to function as a dimer (31), hence the active form is shown as a dimer on the basis of the solution structure of dimeric ALIX-ΔPRR (30).

The structural basis of PRM recognition by ESCRTs and ESCRT-associated proteins. All models are in a ball-and-stick representation, with the PRM peptide colored in brown and protein domains colored in green (except for C and D, where multiple peptides are shown). Key hydrogen bonds between protein domain and peptide are shown as black dashed lines. (A) P(S/T)AP recognition. Structure of human TSG101 UEV domain bound to the human Hrs PSAP peptide (PDB id: 3OBQ). (B) SDP recognition by the yeast Vps23 UEV domain. Structure of the Vps23 UEV domain bound to a yeast SDP peptide (PDB id: 3R42). Water molecules are shown as spheres. (C) The PPXY motif. The structure of human Nedd4 WW-3 domain in complex with ENaC PPNY peptide (PDB id: 1I5H). (D, E) Structural comparison of the ALIX V domain in complex with late-domain peptides of viruses. (D) HIV-1 p6 Gag (PDB id: 2R02, brown) and EIAV p9-Gag (PDB id: 2R03, gray) are overlaid together binding to ALIX V domain. The hydrogen bonds between ALIX and HIV-1 p6 are shown in black dashed lines; The H-bonds between ALIX and EIAV p9 are shown in blue dashed lines. (E) SIV(mac239) p6-Gag peptide (PDB id: 2XS1, blue) and SIV(agmTan-1) p6-Gag (PDB id: 2XS8, light purple) are overlaid together in complex with ALIX V domain. The hydrogen bond between ALIX Asp506 and SIVmac239 Y45 is labeled using black dashed line; The hydrogen bonds between ALIX and SIV(agmTan-1) are shown in magenta dashed line. (F) ALIX GPPX3Y peptide bound to CEP55 (PDB id: 3E1R). (G) ALIX PPR peptide interacts with ALG-2 (PDB id: 2ZNE). Protein chain A and peptide chain C are shown here, Zn²⁺ ions are shown as spheres. The sticks of Y806, Y809 and Y812 in ALIX PRR peptide are shown in a transparent model in order to highlight the backbone conformation of the ALIX PRR peptide.