As a transcription factor, GLI1 plays an important role in cell cycle regulation, DNA replication, and DNA damage responses. The aberrant activation of GLI1 has been associated with cancers such as glioma, osteosarcoma, and rhabdomyosarcoma. The binding of GLI1 to a specific DNA sequence was achieved by five tandem zinc finger motifs (Zif motifs) on the N-terminal part of the molecule. Here, we reported a novel homodimeric crystal structure of Zif1-2. These two Zif motifs are linearized. Namely, Zif2 does not bend and interact with Zif1 of the same molecule. Instead, Zif1 from one molecule interacts with Zif2 from another molecule. The dimer interface of Zif1-2 is unique and different from the conformation of Zif1-2 from the GLI1-DNA co-crystal structure. The dimeric conformation of Zif motifs could represent the native conformation of apo form GLI1 Zif motifs in the cell. The molecular dynamics simulation result of the homodimer, the in silico mutagenesis, and the predicted protease stability of these mutants using a large language model are also presented.

Glioblastoma multiform (GBM) is the most aggressive and prevalent form of brain cancer, with average survival expected to be less than two years from diagnosis. GBM affects the glial cells of the central nervous system causing damage to regular brain function including memory, hearing, and vision. Current therapeutics are associated with dangerous complications, such as

Glioblastoma multiform (GBM) is the most aggressive and prevalent form of brain cancer, with average survival expected to be less than two years from diagnosis. GBM affects the glial cells of the central nervous system causing damage to regular brain function including memory, hearing, and vision. Current therapeutics are associated with dangerous complications, such as

Glioblastoma multiform (GBM) is the most aggressive and prevalent form of brain cancer, with average survival expected to be less than two years from diagnosis. GBM affects the glial cells of the central nervous system causing damage to regular brain function including memory, hearing, and vision. Current therapeutics are associated with dangerous complications, such as

Glioblastoma multiform (GBM) is the most aggressive and prevalent form of brain cancer, with average survival expected to be less than two years from diagnosis. GBM affects the glial cells of the central nervous system causing damage to regular brain function including memory, hearing, and vision. Current therapeutics are associated with dangerous complications, such as