The mechanisms that underlie the spontaneous and faithful assembly of virus particles are guiding the design of self-assembling protein-based nanostructures for biomedical or nanotechnological uses. In this study, the human immunodeficiency virus (HIV-1) capsid was used as a model to investigate what molecular feature(s) may determine whether a protein nanoparticle with the intended architecture, instead of an aberrant particle, will be self-assembled in vitro. Attempts of using the HIV-1 capsid protein CA for achieving in vitro the self-assembly of cone-shaped nanoparticles that contain CA hexamers and pentamers, similar to authentic viral capsids, had typically yielded hexamer-only tubular particles. We hypothesized that a reduction in the stability of a transient major assembly intermediate, a trimer of CA dimers (ToD), will increase the propensity of CA to assemble in vitro into cone-shaped particles instead of tubes. Certain amino acid substitutions at CA-CA interfaces strongly favored in vitro the assembly of cone-shaped nanoparticles that resembled authentic HIV-1 capsids. All-atom MD simulations indicated that ToDs formed by CA mutants with increased propensity for assembly into cone-shaped particles are destabilized relative to ToDs formed by wt CA or by another mutant that assembles into tubes. The results also indicated that ToD destabilization is mediated by conformational distortion of different CA-CA interfaces, which removes some interprotein interactions within the ToD. A model is proposed to rationalize the linkage between reduced ToD stability and increased propensity for the formation of CA pentamers during particle growth in vitro, favoring the assembly of cone-shaped HIV-1 capsid-like nanoparticles.
机构:
Natl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
IPB Univ, Grad Sch, Program Biotechnol, Bogor, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Rosmeita, Chindy Nur
Budiarti, Sri
论文数: 0引用数: 0
h-index: 0
机构:
IPB Univ, Grad Sch, Program Biotechnol, Bogor, Indonesia
IPB Univ, Indonesia Res Ctr Bioresources & Biotechnol, Bogor, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Budiarti, Sri
Mustopa, Apon Zaenal
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Mustopa, Apon Zaenal
Novianti, Ela
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Novianti, Ela
Swasthikawati, Sri
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Swasthikawati, Sri
Chairunnisa, Sheila
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Chairunnisa, Sheila
Hertati, Ai
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Hertati, Ai
Nurfatwa, Maritsa
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Nurfatwa, Maritsa
Ekawati, Nurlaili
论文数: 0引用数: 0
h-index: 0
机构:
Natl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia
Ekawati, Nurlaili
Hasan, Nurhasni
论文数: 0引用数: 0
h-index: 0
机构:
Univ Hasanuddin, Fac Pharm, Jl Perintis Kemerdekaan Km 10, Makassar 90245, IndonesiaNatl Res & Innovat Agcy BRIN, Res Org Life Sci & Environm, Res Ctr Genet Engn, Bogor 16911, Indonesia