Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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CSP Cold shock protein domain

SMART accession number:	SM00357
Description:	RNA-binding domain that functions as a RNA-chaperone in bacteria and is involved in regulating translation in eukaryotes. Contains sub-family of RNA-binding domains in the Rho transcription termination factor.
Interpro abstract (IPR011129):	A conserved domain of about 70 amino acids has been found in prokaryotic and eukaryotic single-strand nucleic-acid binding proteins [ (PUBMED:1622933) (PUBMED:2184368) (PUBMED:8022259) (PUBMED:9586995) (PUBMED:10446180) ]. This domain, which is known as the 'cold-shock domain' (CSD) is present in the proteins listed below. Escherichia coli protein CS7.4 (gene cspA) which is induced in response to low temperature (cold-shock protein) and which binds to and stimulates the transcription of the CCAAT-containing promoters of the HN-S protein and of gyrA. Transcription termination factor Rho, a prokaryotic protein which facilitates transcription termination. Mammalian Y box binding protein 1 (YB1). A protein that binds to the CCAAT-containing Y box of mammalian HLA class II genes. Xenopus Y box binding proteins -1 and -2 (Y1 and Y2). Proteins that bind to the CCAAT-containing Y box of Xenopus hsp70 genes. Xenopus B box binding protein (YB3). YB3 binds the B box promoter element of genes transcribed by RNA polymerase III. Enhancer factor I subunit A (EFI-A) (dbpB). A protein that also bind to CCAAT-motif in various gene promoters. DbpA, a human DNA-binding protein of unknown specificity. Bacillus subtilis cold-shock proteins cspB and cspC. Streptomyces clavuligerus protein SC 7.0. E. coli proteins cspB, cspC, cspD, cspE and cspF. Unr, a mammalian gene encoded upstream of the N-ras gene. Unr contains nine repeats that are similar to the CSD domain. The function of Unr is not yet known but it could be a multivalent DNA-binding protein. PPPin, a mammalian brain-specific protein that binds to histone mRNA and which is thought to play a role in the regulation of brain development.
GO function:	nucleic acid binding (GO:0003676)
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 80336 CSP domains in 70472 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing CSP domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with CSP domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing CSP domain in the selected taxonomic class.

• Cellular role (predicted cellular role)

• Binding / catalysis: RNA-binding

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Bogden CE, Fass D, Bergman N, Nichols MD, Berger JM
  • The structural basis for terminator recognition by the Rho transcription termination factor.
  • Mol Cell. 1999; 3: 487-93
  • Display abstract

  • The E. coli Rho protein disengages newly transcribed RNA from its DNA template, helping terminate certain transcripts. We have determined the X-ray crystal structure of the RNA-binding domain of Rho complexed to an RNA ligand. Filters that screen both ligand size and chemical functionality line the primary nucleic acid-binding site, imparting sequence specificity to a generic single-stranded nucleic acid-binding fold and explaining the preference of Rho for cytosine-rich RNA. The crystal packing reveals two Rho domain protomers bound to a single RNA with a single base spacer, suggesting that the strong RNA-binding sites of Rho may arise from pairing of RNA-binding modules. Dimerization of symmetric subunits on an asymmetric ligand is developed as a model for allosteric control in the action of the intact Rho hexamer.

  • Allison TJ, Wood TC, Briercheck DM, Rastinejad F, Richardson JP, Rule GS
  • Crystal structure of the RNA-binding domain from transcription termination factor rho.
  • Nat Struct Biol. 1998; 5: 352-6
  • Display abstract

  • Transcription termination factor rho is an ATP-dependent hexameric helicase found in most eubacterial species. The Escherichia coli rho monomer consists of two domains, an RNA-binding domain (residues 1-130) and an ATPase domain (residues 131-419). The ATPase domain is homologous to the beta subunit of F1-ATPase. Here, we report that the crystal structure of the RNA-binding domain of rho (rho130) at 1.55 A confirms that rho130 contains the oligosaccharide/oligonucleotide-binding (OB) fold, a five stranded beta-barrel. The beta-barrel of rho130 is also surprisingly similar to the N-terminal beta-barrel of F1 ATPase, extending the applicability of F1 ATPase as a structural model for hexameric rho.

  • Briercheck DM, Wood TC, Allison TJ, Richardson JP, Rule GS
  • The NMR structure of the RNA binding domain of E. coli rho factor suggests possible RNA-protein interactions.
  • Nat Struct Biol. 1998; 5: 393-9
  • Display abstract

  • Rho protein is an essential hexameric RNA-DNA helicase that binds nascent mRNA transcripts and terminates transcription in a wide variety of eubacterial species. The NMR solution structure of the RNA binding domain of rho, rho130, is presented. This structure consists of two sub-domains, an N-terminal three-helix bundle and a C-terminal beta-barrel that is structurally similar to the oligosaccharide/oligonucleotide binding (OB) fold. Chemical shift changes of rho130 upon RNA binding and previous mutagenetic analyses of intact rho suggest that residues Asp 60, Phe 62, Phe 64, and Arg 66 are critical for binding and support the hypothesis that ssRNA/ssDNA binding is localized in the beta-barrel sub-domain. On the basis of these studies and the tertiary structure of rho130, we propose that residues Asp 60, Phe 62, Phe 64, Arg 66, Tyr 80, Lys 105, and Arg 109 participate in RNA-protein interactions.

  • Graumann PL, Marahiel MA
  • A superfamily of proteins that contain the cold-shock domain.
  • Trends Biochem Sci. 1998; 23: 286-90
  • Display abstract

  • Members of a family of cold-shock proteins (CSPs) are found throughout the eubacterial domain and appear to function as RNA-chaperones. They have been implicated in various cellular processes, including adaptation to low temperatures, cellular growth, nutrient stress and stationary phase. The discovery of a domain--the cold-shock domain--that shows strikingly high homology and similar RNA-binding properties to CSPs in a growing number of eukaryotic nucleic-acid-binding proteins suggests that these proteins have an ancient origin.

  • Markus MA, Gerstner RB, Draper DE, Torchia DA
  • The solution structure of ribosomal protein S4 delta41 reveals two subdomains and a positively charged surface that may interact with RNA.
  • EMBO J. 1998; 17: 4559-71
  • Display abstract

  • S4 is one of the first proteins to bind to 16S RNA during assembly of the prokaryotic ribosome. Residues 43-200 of S4 from Bacillus stearothermophilus (S4 Delta41) bind specifically to both 16S rRNA and to a pseudoknot within the alpha operon mRNA. As a first step toward understanding how S4 recognizes and organizes RNA, we have solved the structure of S4 Delta41 in solution by multidimensional heteronuclear nuclear magnetic resonance spectroscopy. The fold consists of two globular subdomains, one comprised of four helices and the other comprised of a five-stranded antiparallel beta-sheet and three helices. Although cross-linking studies suggest that residues between helices alpha2 and alpha3 are close to RNA, the concentration of positive charge along the crevice between the two subdomains suggests that this could be an RNA-binding site. In contrast to the L11 RNA-binding domain studied previously, S4 Delta41 shows no fast local motions, suggesting that it has less capacity for refolding to fit RNA. The independently determined crystal structure of S4 Delta41 shows similar features, although there is small rotation of the subdomains compared with the solution structure. The relative orientation of the subdomains in solution will be verified with further study.

  • Schindelin H, Marahiel MA, Heinemann U
  • Universal nucleic acid-binding domain revealed by crystal structure of the B. subtilis major cold-shock protein.
  • Nature. 1993; 364: 164-8
  • Display abstract

  • The cold-shock response in both Escherichia coli and Bacillus subtilis is induced by an abrupt downshift in growth temperature. It leads to the increased production of the major cold-shock proteins, CS7.4 and CspB, respectively. CS7.4 is a transcriptional activator of two genes. CS7.4 and CspB share 43 per cent sequence identity with the nucleic acid-binding domain of the eukaryotic gene-regulatory Y-box factors. This cold-shock domain is conserved from bacteria to man and contains the RNA-binding RNP1 sequence motif. As a prototype of the cold-shock domain, the structure of CspB has been determined here from two crystal forms. In both, CspB is present as an antiparallel five-stranded beta-barrel. Three consecutive beta-strands, the central one containing the RNP1 motif, create a surface rich in aromatic and basic residues that are presumably involved in nucleic acid binding. Preferential binding of CspB to single-stranded DNA is observed in gel retardation experiments.

  • Schnuchel A et al.
  • Structure in solution of the major cold-shock protein from Bacillus subtilis.
  • Nature. 1993; 364: 169-71
  • Display abstract

  • The cold-shock domain (CSD) is found in many eukaryotic transcriptional factors and is responsible for the specific binding to DNA of a cis-element called the Y-box. The same domain exists in the sequence of the Xenopus RNA-binding proteins FRG Y1 and FRG Y2 (refs 1, 3). The major cold-shock proteins of Escherichia coli (CS7.4) and B. subtilis (CspB) have sequences that are more than 40 per cent identical to the cold-shock domain. We present here the three-dimensional structure of CspB determined by nuclear magnetic resonance spectroscopy. The 67-residue protein consists of an antiparallel five-stranded beta-barrel with strands connected by turns and loops. The structure resembles that of staphylococcal nuclease and the gene-5 single-stranded-DNA-binding protein. A three-stranded beta-sheet, which contains the conserved RNA-binding motif RNP1 as well as a motif similar to RNP2 in two neighbouring antiparallel beta-strands, has basic and aromatic residues at its surface which could serve as a binding site for single-stranded DNA. CspB binds to single-stranded DNA in gel retardation experiments.

  • Jones PG, VanBogelen RA, Neidhardt FC
  • Induction of proteins in response to low temperature in Escherichia coli.
  • J Bacteriol. 1987; 169: 2092-5
  • Display abstract

  • When the growth temperature of an exponential culture of Escherichia coli is abruptly decreased from 37 to 10 degrees C, growth stops for several hours before a new rate of growth is established. During this growth lag the number of proteins synthesized is dramatically reduced, and at one point only about two dozen proteins are made; 13 of these are made at differential rates that are 3 to 300 times increased over the rates at 37 degrees C. The protein with the highest rate of synthesis during the lag is not detectably made at 37 degrees C. The identities of several of these cold shock proteins correlate with previous observations that indicate a block in translation initiation at low temperatures.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 54.55 map04530 Tight junction 9.09 map00260 Glycine, serine and threonine metabolism 9.09 map00970 Aminoacyl-tRNA biosynthesis 9.09 map00670 One carbon pool by folate 9.09 map00271 Methionine metabolism 9.09 map00300 Lysine biosynthesis This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with CSP domain which could be assigned to a KEGG orthologous group, and not all proteins containing CSP domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of CSP domains in PDB

  PDB code	Main view	Title
  1a62		CRYSTAL STRUCTURE OF THE RNA-BINDING DOMAIN OF THE TRANSCRIPTIONAL TERMINATOR PROTEIN RHO
  1a63		THE NMR STRUCTURE OF THE RNA BINDING DOMAIN OF E.COLI RHO FACTOR SUGGESTS POSSIBLE RNA-PROTEIN INTERACTIONS, 10 STRUCTURES
  1a8v		STRUCTURE OF THE RNA-BINDING DOMAIN OF THE RHO TRANSCRIPTION TERMINATOR
  1c9o		CRYSTAL STRUCTURE ANALYSIS OF THE BACILLUS CALDOLYTICUS COLD SHOCK PROTEIN BC-CSP
  1csp		CRYSTAL STRUCTURE OF THE BACILLUS SUBTILIS MAJOR COLD SHOCK PROTEIN, CSPB: A UNIVERSAL NUCLEIC-ACID BINDING DOMAIN
  1csq		CRYSTAL STRUCTURE OF THE BACILLUS SUBTILIS MAJOR COLD SHOCK PROTEIN, CSPB: A UNIVERSAL NUCLEIC-ACID BINDING DOMAIN
  1g6p		SOLUTION NMR STRUCTURE OF THE COLD SHOCK PROTEIN FROM THE HYPERTHERMOPHILIC BACTERIUM THERMOTOGA MARITIMA
  1h95		Solution structure of the single-stranded DNA-binding Cold Shock Domain (CSD) of human Y-box protein 1 (YB1) determined by NMR (10 lowest energy structures)
  1hz9		BACILLUS CALDOLYTICUS COLD-SHOCK PROTEIN MUTANTS TO STUDY DETERMINANTS OF PROTEIN STABILITY
  1hza		BACILLUS CALDOLYTICUS COLD-SHOCK PROTEIN MUTANTS TO STUDY DETERMINANTS OF PROTEIN STABILITY
  1hzb		BACILLUS CALDOLYTICUS COLD-SHOCK PROTEIN MUTANTS TO STUDY DETERMINANTS OF PROTEIN STABILITY
  1hzc		BACILLUS CALDOLYTICUS COLD-SHOCK PROTEIN MUTANTS TO STUDY DETERMINANTS OF PROTEIN STABILITY
  1i5f		BACILLUS CALDOLYTICUS COLD-SHOCK PROTEIN MUTANTS TO STUDY DETERMINANTS OF PROTEIN STABILITY
  1mjc		CRYSTAL STRUCTURE OF CSPA, THE MAJOR COLD SHOCK PROTEIN OF ESCHERICHIA COLI
  1nmf		MAJOR COLD-SHOCK PROTEIN, NMR, 20 STRUCTURES
  1nmg		MAJOR COLD-SHOCK PROTEIN, NMR, MINIMIZED AVERAGE STRUCTURE
  1pv4		X-ray crystal structure of the Rho transcription termination factor in complex with single stranded DNA
  1pvo		X-ray crystal structure of Rho transcription termination factor in complex with ssRNA substrate and ANPPNP
  1wfq		Solution structure of the first cold-shock domain of the human KIAA0885 protein (UNR protein)
  1x65		Solution structure of the third cold-shock domain of the human KIAA0885 protein (UNR PROTEIN)
  1xpo		Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic bicyclomycin
  1xpr		Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic 5a-formylbicyclomycin (FB)
  1xpu		Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic 5a-(3-formylphenylsulfanyl)-dihydrobicyclomycin (FPDB)
  2a8v		RHO TRANSCRIPTION TERMINATION FACTOR/RNA COMPLEX
  2bh8		Combinatorial Protein 1b11
  2es2		Crystal Structure Analysis of the Bacillus Subtilis Cold Shock Protein Bs-CspB in Complex with Hexathymidine
  2f52		Solution structure of cold shock protein CspB from Bacillus subtilis in complex with heptathymidine
  2hax		Crystal structure of Bacillus caldolyticus cold shock protein in complex with hexathymidine
  2ht1		The closed ring structure of the Rho transcription termination factor in complex with nucleic acid in the motor domains
  2i5l		Crystal structure of Bacillus subtilis Cold Shock Protein variant Bs-CspB M1R/E3K/K65I
  2i5m		Crystal structure of Bacillus subtilis cold shock protein CspB variant A46K S48R
  2id0		Escherichia coli RNase II
  2ix0		RNase II
  2ix1		RNase II D209N mutant
  2k5n		Solution NMR Structure of the N-Terminal Domain of Protein ECA1580 from Erwinia carotovora, Northeast Structural Genomics Consortium Target EwR156A
  2kcm		Solution NMR structure of the N-terminal OB-domain of SO_1732 from Shewanella oneidensis. Northeast Structural Genomics Consortium Target SoR210A.
  2l15		Solution Structure of Cold Shock Protein CspA Using Combined NMR and CS-Rosetta method
  2lss		Solution structure of the R. rickettsii cold shock-like protein
  2lxj		Backbone 1H, 13C, and 15N Chemical Shift Assignments for cold shock protein, LmCsp with dT7
  2lxk		Backbone 1H, 13C, and 15N Chemical Shift Assignments for cold shock protein, LmCsp
  2mo0		2MO0
  2mo1		2MO1
  2mqh		2MQH
  2n49		2N49
  2ytv		Solution structure of the fifth cold-shock domain of the human KIAA0885 protein (unr protein)
  2ytx		Solution structure of the second cold-shock domain of the human KIAA0885 protein (UNR protein)
  2yty		Solution structure of the fourth cold-shock domain of the human KIAA0885 protein (UNR protein)
  3a0j		Crystal structure of cold shock protein 1 from Thermus thermophilus HB8
  3aqq		Crystal structure of human CRHSP-24
  3cam		Crystal structure of the cold shock domain protein from Neisseria meningitidis
  3i2z		Structure of cold shock protein E from Salmonella typhimurium
  3ice		Rho transcription termination factor bound to RNA and ADP-BeF3
  3l0o		Structure of RNA-free Rho transcription termination factor from Thermotoga maritima
  3mef		MAJOR COLD-SHOCK PROTEIN FROM ESCHERICHIA COLI SOLUTION NMR STRUCTURE
  3pf4		Crystal structure of Bs-CspB in complex with r(GUCUUUA)
  3pf5		Crystal structure of Bs-CspB in complex with rU6
  3trz		Mouse Lin28A in complex with let-7d microRNA pre-element
  3ts0		Mouse Lin28A in complex with let-7f-1 microRNA pre-element
  3ts2		Mouse Lin28A in complex with let-7g microRNA pre-element
  3ulj		Crystal structure of apo Lin28B cold shock domain
  4a4i		Crystal structure of the human Lin28b cold shock domain
  4a75		The Lin28b Cold shock domain in complex with hexathymidine.
  4a76		The Lin28b Cold shock domain in complex with heptathymidine
  4alp		The Lin28b Cold shock domain in complex with hexauridine
  4qqb		4QQB
  5jji		5JJI
  5jjk		5JJK
  5jjl		5JJL

• Links (links to other resources describing this domain)

• PFAM	CSD
  INTERPRO	IPR011129
  PROSITE	COLD_SHOCK

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