Angiogenic Tyrosyl t-RNA Synthetase Compositions and Methods

摘要

The present invention provides an isolated tyrosyl tRNA synthetase (TyrRS) polypeptide variant which comprises (a) a Rossmann fold region or a portion thereof, preferably including an α5 coil; and (b) an anticodon recognition domain or portion thereof, preferably including an α14 coil. Preferably, the α5 coil and the α14 coil have a greater spatial separation in the tertiary structure of the variant compared to the corresponding spatial separation in native human TyrRS. The variant preferably comprises an amino acid residue sequence identity of at least about 50% compared to the amino acid residue sequence of human TyrRS (SEQ ID NO: 3), includes at least one non-conservative amino acid residue substitution relative to the amino acid residue sequence of human TyrRS, and preferably presents an exposed ELR motif in the α5 coil on an external portion of the tertiary structure of the polypeptide. A preferred TyrRS protein variant comprises the amino acid residue sequence of SEQ ID NO: 4 or a portion thereof. The proteins and protein fragments of the invention are angiogenic and are useful for stimulating angiogenesis in mammalian tissues.