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Engineering small molecules that nucleate assembly of protein complexes
Author(s) -
Ansari Aseem Z.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.411.2
Subject(s) - transcription factor , transcription (linguistics) , microbiology and biotechnology , modular design , multiprotein complex , computational biology , eukaryotic transcription , chemistry , dna , synthetic biology , context (archaeology) , biology , gene , gene expression , biochemistry , computer science , promoter , operating system , paleontology , philosophy , linguistics
Cooperative assembly permits weak interactions between components of the gene expression machinery to be harnessed together in the creation of a multicomponent complex of high affinity and exquisite specificity. In the context of transcription factors, weak molecular interactions between transcription factors facilitate the assembly of multiprotein complexes. These complexes present multiple activation modules thereby nucleating the assembly of the transcriptional machinery. The modular nature of transcription factors lends itself to creation of ligands that utilize multivalent cooperative interactions to enhance binding affinity and specificity. We will present our design of synthetic Hox mimics that cooperatively stabilize the assembly of cellular transcription factor to a targeted DNA sequence. Our modular design can be broadly applied to engineer molecules that nucleate the assembly of other transcription factors. These molecules can then be used to modulate gene networks and thereby regulate cell fate.