The Truncated C-terminal RNA Recognition Motif of TDP-43 Protein Plays a Key Role in Forming Proteinaceous
نویسندگان
چکیده
Yi-Ting Wang, Pan-Hsien Kuo, Chien-Hao Chiang, Jhe-Ruei Liang, Yun-Ru Chen , Shuying Wang**, James C. K. Shen, and Hanna S. Yuan From the Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, the Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsin Chu 30013, Taiwan, the Department of Life Sciences, Institute of Genome Sciences, National Yang-Ming University, Taipei 11221, Taiwan, the Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan, the **Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70457, Taiwan, the Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 70457, Taiwan, and the Graduate Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei 10048, Taiwan
منابع مشابه
The Truncated C-terminal RNA Recognition Motif of TDP-43 Protein Plays a Key Role in Forming Proteinaceous Aggregates*
TDP-43 is the major pathological protein identified in the cellular inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The pathogenic forms of TDP-43 are processed C-terminal fragments containing a truncated RNA-recognition motif (RRM2) and a glycine-rich region. Although extensive studies have focused on this protein, it remains unclear how the dimeric full-leng...
متن کاملRNP2 of RNA Recognition Motif 1 Plays a Central Role in the Aberrant Modification of TDP-43
Phosphorylated and truncated TAR DNA-binding protein-43 (TDP-43) is a major component of ubiquitinated cytoplasmic inclusions in neuronal and glial cells of two TDP-43 proteinopathies, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Modifications of TDP-43 are thus considered to play an important role in the pathogenesis of TDP-43 proteinopathies. However, both the initial ...
متن کاملStructural insights into TDP-43 in nucleic-acid binding and domain interactions
TDP-43 is a pathogenic protein: its normal function in binding to UG-rich RNA is related to cystic fibrosis, and inclusion of its C-terminal fragments in brain cells is directly linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Here we report the 1.65 A crystal structure of the C-terminal RRM2 domain of TDP-43 in complex with a single-stranded DNA. We s...
متن کاملAn Amyloid-Like Pathological Conformation of TDP-43 Is Stabilized by Hypercooperative Hydrogen Bonds
TDP-43 is an essential RNA-binding protein forming aggregates in almost all cases of sporadic amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal lobar dementia (FTLD) and other neurodegenerative diseases. TDP-43 consists of a folded N-terminal domain with a singular structure, two RRM RNA-binding domains, and a long disordered C-terminal region which plays roles in functional ...
متن کاملRequirements for stress granule recruitment of fused in sarcoma (FUS) and TAR DNA-binding protein of 43 kDa (TDP-43).
Cytoplasmic inclusions containing TAR DNA-binding protein of 43 kDa (TDP-43) or Fused in sarcoma (FUS) are a hallmark of amyotrophic lateral sclerosis (ALS) and several subtypes of frontotemporal lobar degeneration (FTLD). FUS-positive inclusions in FTLD and ALS patients are consistently co-labeled with stress granule (SG) marker proteins. Whether TDP-43 inclusions contain SG markers is current...
متن کامل