Cold shock domains as nucleic acid-binding modules

Cold shock domains are present in bacterial cold shock proteins and several eukaryotic transcriptions factors. They are known to bind DNA and/or RNA single strands and thus integrate the transcription and translation control levels of gene expression regulation. Following earlier work revealing the binding mode of DNA single strands to bacterial cold shock proteins it could be demonstrated that RNA strands share this binding mode by stretching a single strand across a conserved protein surface of the cold shock domain and establishing base contacts at seven distinct sub-sites. For the cold shock protein Bs-CspB we could show that pyrimidine-rich RNA strands bind with tenfold reduced affinity compared to DNA strands of identical sequence. Whereas bacterial cold shock proteins consist of a single cold shock domain, cold shock domains of eukaryotic proteins, such as the transcription/translation factor YB-1 are often associated with natively unfolded polypeptide regions. An exception to this rule is found in the protein Lin28 where a cold shock domain is present along with a tandem zinc-knuckle domain. Lin28 inhibits the maturation of the let-7 microRNA by two different mechanisms. We could demonstrate that Lin28 binds DNA and RNA in a modus resembling the bacterial cold shock proteins and thereby alters the conformation of let-7 precursor RNA in a chaperonin-like fashion.

Ligand binding surface of Bs-CspB and its phylogenetic conservation

Figure adapted from
Sachs, R., Max, K.E., Heinemann, U., Balbach, J.

RNA single strands bind to a conserved surface of the major cold shock protein in crystals and solution
RNA : (2011-11-29)