{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["6"],"submitter":["Jiang LL"],"pubmed_abstract":["TDP-43 is a DNA/RNA binding protein associated with TDP-43 proteinopathies. Many mutations have been identified in the flexible C-terminal region, which is implicated in the disease pathology. We investigated four point mutations in the amyloidogenic core region (residues 311-360) of TDP-43 by biochemical and spectroscopic methods. We found that the G335D mutation enhances the aggregation and inclusion formation of TDP-43 and this mutant in TDP-35 (the C-terminal fragment of 35 kDa) exaggerates the antagonist effect on RNA processing by endogenous TDP-43; whereas Q343R gives an opposite effect. As a comparison, M337V and Q331K have very little impact on the aggregation and inclusion formation of TDP-43 or TDP-35. NMR structural analysis showed that the G335D mutant in the core region forms"],"journal":["Scientific reports"],"pagination":["23928"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4814915"],"repository":["biostudies-literature"],"pubmed_title":["Two mutations G335D and Q343R within the amyloidogenic core region of TDP-43 influence its aggregation and inclusion formation."],"pmcid":["PMC4814915"],"pubmed_authors":["Yang H","He WT","Che MX","Hu HY","Yin XF","Jiang LL","Zhao J"],"additional_accession":[]},"is_claimable":false,"name":"Two mutations G335D and Q343R within the amyloidogenic core region of TDP-43 influence its aggregation and inclusion formation.","description":"TDP-43 is a DNA/RNA binding protein associated with TDP-43 proteinopathies. Many mutations have been identified in the flexible C-terminal region, which is implicated in the disease pathology. We investigated four point mutations in the amyloidogenic core region (residues 311-360) of TDP-43 by biochemical and spectroscopic methods. We found that the G335D mutation enhances the aggregation and inclusion formation of TDP-43 and this mutant in TDP-35 (the C-terminal fragment of 35 kDa) exaggerates the antagonist effect on RNA processing by endogenous TDP-43; whereas Q343R gives an opposite effect. As a comparison, M337V and Q331K have very little impact on the aggregation and inclusion formation of TDP-43 or TDP-35. NMR structural analysis showed that the G335D mutant in the core region forms","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Mar","modification":"2026-04-14T21:21:23.649Z","creation":"2019-03-27T03:10:44Z"},"accession":"S-EPMC4814915","cross_references":{"pubmed":["27030292"],"doi":["10.1038/srep23928"]}}