4g84
From Proteopedia
Crystal structure of human HisRS
Structural highlights
DiseaseHARS1_HUMAN Usher syndrome type 3;Autosomal dominant Charcot-Marie-Tooth disease type 2W. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionHARS1_HUMAN Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP) (PubMed:29235198). Plays a role in axon guidance (PubMed:26072516).[1] [2] Publication Abstract from PubMedAminoacyl-tRNA synthetases (AARSs) catalyze aminoacylation of tRNAs in the cytoplasm. Surprisingly, AARSs also have critical extracellular and nuclear functions. Evolutionary pressure for new functions might be manifested by splice variants that skip only an internal catalytic domain (CD) and link noncatalytic N- and C-terminal polypeptides. Using disease-associated histidyl-tRNA synthetase (HisRS) as an example, we found an expressed 171-amino acid protein (HisRSDeltaCD) that deleted the entire CD, and joined an N-terminal WHEP to the C-terminal anticodon-binding domain (ABD). X-ray crystallography and three-dimensional NMR revealed the structures of human HisRS and HisRSDeltaCD. In contrast to homodimeric HisRS, HisRSDeltaCD is monomeric, where rupture of the ABD's packing with CD resulted in a dumbbell-like structure of flexibly linked WHEP and ABD domains. In addition, the ABD of HisRSDeltaCD presents a distinct local conformation. This natural internally deleted HisRS suggests evolutionary pressure to reshape AARS tertiary and quaternary structures for repurposing. Internally Deleted Human tRNA Synthetase Suggests Evolutionary Pressure for Repurposing.,Xu Z, Wei Z, Zhou JJ, Ye F, Lo WS, Wang F, Lau CF, Wu J, Nangle LA, Chiang KP, Yang XL, Zhang M, Schimmel P Structure. 2012 Sep 5;20(9):1470-7. PMID:22958643[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
Categories: Homo sapiens | Large Structures | Schimmel P | Wei Z | Wu J | Yang X-L | Zhang M | Zhou JJ
