This educational animation, which demonstrates proteins in search of target DNA sequences, was created by Visual Science for Johan Elf laboratory at the University of Uppsala, the oldest university in Scandinavia. The lab studies biophysical foundations of key molecular processes in bacterial cells, such as transcriptional regulation, protein biosynthesis and cell division.
The animation shows two different ways of how proteins search for target sites on the DNA genomic sequence. One variant can be used by transcription factors, and the other, for example, by CRISPR complexes.
The first variant is shown on the example of the Lac repressor dimeric form. This protein is attached to DNA most of the time and slides along that linear molecule, spontaneously changing the direction of motion and occasionally disconnecting, so that after a short diffusion in three-dimensional space it could turn out on another DNA site and continue the one-dimensional sliding. After the identification of the target sequence (part of the operator), the protein changes the conformation and binds to it more firmly, stopping movement.
CRISPR-Cas9 complex most of the time freely moves in the three-dimensional space of the bacterial cytoplasm. The binding with the right DNA sequence (in case of CRISPR-Cas9 complexes it is called protospacer) occurs in two stages. First, the complex recognizes a specific short motif called PAM (protospacer adjacent motif), then it untwists the adjacent region of the DNA. As a result of that the complementarity between this site and the CRISPR-RNA, which is part of the protein complex, is checked. If complementarity is not complete, the complex detaches, continuing the search.
Recently, evidence has been emerging that CRISPR-Cas complexes can also shortly slide along the DNA molecule.
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