Abstract:
Isolated monomelic aminoacyl-tRNA synthetase polypeptides and polynucleotides having non-canonical biological activities are provided, as well as compositions and methods related thereto.
Abstract:
Isolated monomelic aminoacyl-tRNA synthetase polypeptides and polynucleotides having non-canonical biological activities are provided, as well as compositions and methods related thereto.
Abstract:
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.
Abstract translation:本发明提供了分离的酪氨酰tRNA合成酶(TyrRS)多肽变体,其包含(a)Rossmann折叠区或其部分,优选包括α5线圈; 和(b)反密码子识别结构域或其部分,优选包含α14线圈。 优选地,α5线圈和α14线圈在变体的三级结构中具有比天然人TyrRS中相应的空间分离更大的空间分离。 与人TyrRS(SEQ ID NO:3)的氨基酸残基序列相比,该变体优选包含至少约50%的氨基酸残基序列同一性,包括相对于氨基酸至少一个非保守氨基酸残基取代 人TyrRS的残基序列,并且优选在多肽的三级结构的外部部分上在α5线圈中存在暴露的ELR基序。 优选的TyrRS蛋白质变体包含SEQ ID NO:4的氨基酸残基序列或其部分。 本发明的蛋白质和蛋白质片段是血管生成的并且可用于刺激哺乳动物组织中的血管发生。
Abstract:
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.
Abstract translation:本发明提供了分离的酪氨酰tRNA合成酶(TyrRS)多肽变体,其包含(a)Rossmann折叠区域或其部分,优选包括α5线圈; 和(b)反密码子识别结构域或其部分,优选包括α14线圈。 优选地,与天然人TyrRS中的相应空间分离相比,α5线圈和α14线圈在变体的三级结构中具有更大的空间分离。 与人TyrRS(SEQ ID NO:3)的氨基酸残基序列相比,该变体优选包含至少约50%的氨基酸残基序列同一性,包括相对于氨基酸至少一个非保守氨基酸残基取代 人TyrRS的残基序列,并且优选在多肽的三级结构的外部部分上的α5线圈中存在暴露的ELR基序。 优选的TyrRS蛋白质变体包含SEQ ID NO:4的氨基酸残基序列或其部分。 本发明的蛋白质和蛋白质片段是血管生成的并且可用于刺激哺乳动物组织中的血管发生。
Abstract:
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 5 coil; and (b) an anticodon recognition domain or portion thereof, preferably including an 14 coil. Preferably, the 5 coil and the 14 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 sequence of human TyrRS, and preferably presents an exposed ELR motif in the 5 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.
Abstract translation:本发明提供了一种分离的酪氨酰tRNA合成酶(TyrRS)多肽变体,其包含(a)Rossmann折叠区域或其部分,优选包括5个线圈; 和(b)反密码子识别结构域或其部分,优选包含14个线圈。 优选地,与天然人类TyrRS中相应的空间分离相比,5线圈和14线圈在变体的三级结构中具有更大的空间分离。 所述变体优选与人TyrRS(SEQ ID NO:3)的氨基酸残基序列相比具有至少约50%的氨基酸残基序列同一性,包括至少一个人TyrRS的非保守氨基酸残基序列,和 优选在5线圈中在多肽的三级结构的外部部分上呈现暴露的ELR基序。 优选的TyrRS蛋白质变体包含SEQ ID NO:4的氨基酸残基序列或其部分。 本发明的蛋白质和蛋白质片段是血管生成的并且可用于刺激哺乳动物组织中的血管发生。
Abstract:
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 5 coil; and (b) an anticodon recognition domain or portion thereof, preferably including an 14 coil. Preferably, the 5 coil and the 14 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 sequence of human TyrRS, and preferably presents an exposed ELR motif in the 5 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.
Abstract translation:本发明提供了一种分离的酪氨酰tRNA合成酶(TyrRS)多肽变体,其包含(a)Rossmann折叠区域或其部分,优选包括5个线圈; 和(b)反密码子识别结构域或其部分,优选包含14个线圈。 优选地,与天然人类TyrRS中相应的空间分离相比,5线圈和14线圈在变体的三级结构中具有更大的空间分离。 所述变体优选与人TyrRS(SEQ ID NO:3)的氨基酸残基序列相比具有至少约50%的氨基酸残基序列同一性,包括至少一个人TyrRS的非保守氨基酸残基序列,和 优选在5线圈中在多肽的三级结构的外部部分上呈现暴露的ELR基序。 优选的TyrRS蛋白质变体包含SEQ ID NO:4的氨基酸残基序列或其部分。 本发明的蛋白质和蛋白质片段是血管生成的并且可用于刺激哺乳动物组织中的血管发生。