PROSITE documentation PDOC00304

Cold-shock (CSD) domain profile

The cold-shock domain (CSD) is an ancient β-barrel fold of about 70 amino acids that binds single-stranded nucleic acids (both RNA and DNA). CSD-containing proteins have been found in all three domains of life and function in a variety of processes that are related, for the most part, to post-translational gene regulation. CSDs were first found in bacterial cold-shock proteins (CSPs). CSPs are small, abundant proteins that are essentially composed of one CSD. Some members of this family are strongly induced after cold shock and are involved in adaptation to low temperatures, while others function during normal growth conditions. Bacterial CSPs bind to single-stranded nucleic acids and function as RNA chaperones, rescuing RNAs trapped in unproductive folding states. This general molecular function enables CSPs to participate in the regulation of practically any step of gene expression involving RNA, including transcription, translation, and RNA turnover. Since their discovery in bacterial CSPs, CSDs have been found in many other bacterial and eukaryotic proteins. In multicellular organisms, CSDs are usually embedded in larger proteins [1,2,3,4,5].

The CSD adopts a five-stranded antiparallel β-barrel structure, which is similar to the oligonucleotide/oligosaccharide fold (OB-fold) (see <PDB:1WFQ>). Many CSDs contain the motifs [YF]-G-F-I and [VF]-[VF]-H, which are known as the ribonucleoprotein (RNP)-1 and RNP-2 motifs and include most of the residues involved in the interaction with nucleic acids. RNP-1 and RNP-2 are located in strands β2 and β3, respectively [2,3,4,6].

Some proteins known to contain a CSD domain are listed below:

• Bacterial cold-shock proteins (CSPs), regulate the cellular response to temperature downshift. Their general principle of function involves RNA chaperoning and transcriptional antitermination.
• Plant glycine-rich protein 2 (GRP2), a nucleo-cytoplasmic factor with RNA chaperone activity that functions under cold stress, in addition to being required for flower and seed development. GRP2 contains one CSD, two glycine-rich domains, and two CCHC zinc-fingers (see <PDOC50158>).
• Chordate DNA-binding protein A (DBPA, also known as CSDA), represses the transcription of several genes, occasionally in conjunction with YB-1.
• Chordate DNA-binding protein B (DBPB), commonly referred to as Y-box- binding factor 1 (YB-1), a DNA-binding protein that recognizes the Y-box sequence present in major histocompatibility complex class II promoters.
• Chordate DNA-binding protein C (DBPC) (frog germ-cell-specific Y-box protein 2, FRGY2), a major component of maternally stored RNPs in Xenopus oocytes. FRGY2 packages the mRNA into compact RNPs leading to translational repression and mRNA stabilization.
• Caenorhabditis elegans protein Lin-28 (abnormal cell lineage 28), a small cytoplamsic protein that, in addition one CSD, contains two CCHC zinc finger motifs that cooperate with the CSD in target recognition. Lin-28 regulates microRNA (miRNA) metabolism.
• Animal Lin-28 homologs.
• Metazoan UNR (upstream of N-ras), known as CSDE1 in mammals. UNR is a conserved cytoplasmic RNA binding protein with roles in the regulation of mRNA stability and translation. It is unique within the eukaryotic CSD protein family in that it contains five copies of the CSD. The CSDs of UNR have a function in protein and nucleic acid binding.

We developed both a pattern and a profile for the CSD domain. As a signature pattern for the CSD domain we selected its most conserved region which is located in its N-terminal section and corresponds to the RNP-1 RNA-binding motif [6]. The profile we developed covers the CSD domain.