title: Coupling protein stability and protein function in Escherichia coli CspA.
abstract: BACKGROUND
  CspA is a small protein that binds single-stranded RNA and DNA. The binding site of CspA consists of a cluster of aromatic amino acids, which form an unusually large nonpolar patch on the surface of the protein. Because nonpolar residues are generally found in the interiors of proteins, this cluster may have evolved to bind nucleic acids at the expense of protein stability.
  
  
  RESULTS
  Three neighboring phenylalanines have been mutated singly and in combination to leucine and to serine. All mutations adversely affect DNA binding. Surprisingly, all mutations, and especially those to serine, are destabilizing.
  
  
  CONCLUSIONS
  The aromatic cluster in CspA is required not only for protein function but also for protein stability. This result is pertinent to the design of beta-sheet proteins and single-stranded nucleic acid binding proteins, whose binding mode is proposed to be of aromatic-aromatic intercalation.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Hillier
authors.forename: H M
authors.initials: HM
authors.lastname: Rodriguez
authors.forename: L M
authors.initials: LM
authors.lastname: Gregoret
mesh_terms: D001426:Bacterial Proteins; D001665:Binding Sites / Q000235:genetics; D002942:Circular Dichroism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D016254:Mutagenesis, Insertional / Q000235:genetics; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D014508:Urea / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; C099484:CspA protein, Bacillus; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D016601:RNA-Binding Proteins; D014508:Urea