Guest-host crosstalk in an angiogenin-RNase A chimeric protein.
Angiogenin and ribonuclease A share 33% sequence identity but have distinct functions. Angiogenin is a potent inducer of angiogenesis that is only weakly ribonucleolytic, whereas ribonuclease A is a robust ribonuclease that is not angiogenic. A chimera ("ARH-I"), in which angiogenin residues 58-70 are replaced with residues 59-73 of ribonuclease A, has intermediate ribonucleolytic potency and no angiogenic activity. Here we report a crystal structure of ARH-I that reveals the molecular basis for these characteristics. The ribonuclease A-derived (guest) segment adopts a structure largely similar to that in ribonuclease A, and successfully converts this region from a cell-binding site to a purine-binding site. At the same time, its presence causes complex changes in the angiogenin-derived (host) portion that account for much of the increased ribonuclease activity of ARH-I. Guest-host interactions of this type probably occur more generally in protein chimeras, emphasizing the importance of direct structural information for understanding the functional behavior of such molecules.
Holloway
Daniel E
DE
Department of Biology and Biochemistry, South Building, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
Shapiro
Robert
R
Hares
Michelle C
MC
Leonidas
Demetres D
DD
Acharya
K Ravi
KR
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D002417:Cattle; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D017510:Protein Folding; D011743:Pyrimidines / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D010446:Peptide Fragments; D011743:Pyrimidines; D011993:Recombinant Fusion Proteins; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; C030986:pyrimidine