Download MendeleyGuest-Host Crosstalk in an Angiogenin-RNase A Chimeric Protein
Holloway, D.E., Shapiro, R., Hares, M.C., Leonidas, D.D., Acharya, K.R.(2002) Biochemistry 41: 10482
- PubMed: 12173935
- DOI: https://doi.org/10.1021/bi026151r
- Primary Citation of Related Structures:
1GV7 - PubMed Abstract:
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.
Organizational Affiliation:
Department of Biology and Biochemistry, South Building, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
