5w3n
From Proteopedia
Molecular structure of FUS low sequence complexity domain protein fibrils
Structural highlights
DiseaseFUS_HUMAN Frontotemporal dementia with motor neuron disease;Hereditary essential tremor;Amyotrophic lateral sclerosis;Juvenile amyotrophic lateral sclerosis;Myxofibrosarcoma;Myxoid/round cell liposarcoma. A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. The disease may be caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionFUS_HUMAN Binds both single-stranded and double-stranded DNA and promotes ATP-independent annealing of complementary single-stranded DNAs and D-loop formation in superhelical double-stranded DNA. May play a role in maintenance of genomic integrity. Publication Abstract from PubMedPolymerization and phase separation of proteins containing low-complexity (LC) domains are important factors in gene expression, mRNA processing and trafficking, and localization of translation. We have used solid-state nuclear magnetic resonance methods to characterize the molecular structure of self-assembling fibrils formed by the LC domain of the fused in sarcoma (FUS) RNA-binding protein. From the 214-residue LC domain of FUS (FUS-LC), a segment of only 57 residues forms the fibril core, while other segments remain dynamically disordered. Unlike pathogenic amyloid fibrils, FUS-LC fibrils lack hydrophobic interactions within the core and are not polymorphic at the molecular structural level. Phosphorylation of core-forming residues by DNA-dependent protein kinase blocks binding of soluble FUS-LC to FUS-LC hydrogels and dissolves phase-separated, liquid-like FUS-LC droplets. These studies offer a structural basis for understanding LC domain self-assembly, phase separation, and regulation by post-translational modification. Structure of FUS Protein Fibrils and Its Relevance to Self-Assembly and Phase Separation of Low-Complexity Domains.,Murray DT, Kato M, Lin Y, Thurber KR, Hung I, McKnight SL, Tycko R Cell. 2017 Oct 19;171(3):615-627.e16. doi: 10.1016/j.cell.2017.08.048. Epub 2017 , Sep 21. PMID:28942918[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
Categories: Homo sapiens | Large Structures | Hung I | Kato M | Lin Y | McKnight S | Murray DT | Thurber K | Tycko R
