Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications

Konstantina Kazakou, Daniel E Holloway, S H Prior, Vasanta Subramanian, K Ravi Acharya

Research output: Contribution to journalArticlepeer-review

22 Citations (SciVal)


The widespread and functionally varied members of the ribonuclease A (RNase A) superfamily provide an excellent opportunity to study evolutionary forces at work on a conserved protein scaffold. Representatives from the zebrafish are of particular interest as the evolutionary distance from non-ichthyic homologues is large. We conducted an exhaustive survey of available zebrafish DNA sequences and found significant polymorphism among its four known homologues. In an extension of previous nomenclature, the variants have been named RNases ZF-1a-c,-2a-d,-3a-e and-4. We present the first X-ray crystal structures of zebrafish ribonucleases, RNases ZF-1a and-3e at 1.35-and 1.85 angstrom resolution, respectively. Structure-based clustering with ten other ribonuclease structures indicates greatest similarity to mammalian angiogenins and amphibian ribonucleases, and supports the view that all present-day ribonucleases evolved from a progenitor with three disulphide bonds. In their details, the two structures are intriguing melting-pots of features present in ribonucleases from other vertebrate classes. Whereas in RNase ZF-1a the active site is obstructed by the C-terminal segment (as observed in angiogenin), in RNase ZF-3e the same region is open (as observed in more catalytically efficient homologues). The progenitor of present-day ribonucleases is more likely to have had an obstructive C terminus, and the relatively high similarity (late divergence) of RNases ZF-1 and-3 infers that the active site unblocking event has happened independently in different vertebrate lineages.
Original languageEnglish
Pages (from-to)206-222
Number of pages17
JournalJournal of Molecular Biology
Issue number1
Early online date3 May 2008
Publication statusPublished - 27 Jun 2008


  • angiogenin
  • protein evolution
  • rnase-a
  • ribonuclease
  • human angiogenin
  • protein-structure alignment
  • amyotrophic-lateral-sclerosis
  • escherichia-coli
  • X-ray crystallography
  • active-site
  • enzymatic potency
  • zebrafish
  • eosinophil-derived neurotoxin
  • pancreatic ribonuclease
  • x-ray-structure


Dive into the research topics of 'Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications'. Together they form a unique fingerprint.

Cite this