TGF beta-induced protein/periostin / EMI domain / EMI domain profile. / FAS1 domain / FAS1 domain superfamily / Fasciclin domain / FAS1/BIgH3 domain profile. / Four repeated domains in the Fasciclin I family of proteins, present in many other contexts. 類似検索 - ドメイン・相同性
Transforming growth factor-beta-induced protein ig-h3 類似検索 - 構成要素
ジャーナル: Commun Biol / 年: 2023 タイトル: Release of frustration drives corneal amyloid disaggregation by brain chaperone. 著者: Jia Yi Kimberly Low / Xiangyan Shi / Venkatraman Anandalakshmi / Dawn Neo / Gary Swee Lim Peh / Siew Kwan Koh / Lei Zhou / M K Abdul Rahim / Ketti Boo / JiaXuan Lee / Harini Mohanram / Reema ...著者: Jia Yi Kimberly Low / Xiangyan Shi / Venkatraman Anandalakshmi / Dawn Neo / Gary Swee Lim Peh / Siew Kwan Koh / Lei Zhou / M K Abdul Rahim / Ketti Boo / JiaXuan Lee / Harini Mohanram / Reema Alag / Yuguang Mu / Jodhbir S Mehta / Konstantin Pervushin / 要旨: TGFBI-related corneal dystrophy (CD) is characterized by the accumulation of insoluble protein deposits in the corneal tissues, eventually leading to progressive corneal opacity. Here we show that ...TGFBI-related corneal dystrophy (CD) is characterized by the accumulation of insoluble protein deposits in the corneal tissues, eventually leading to progressive corneal opacity. Here we show that ATP-independent amyloid-β chaperone L-PGDS can effectively disaggregate corneal amyloids in surgically excised human cornea of TGFBI-CD patients and release trapped amyloid hallmark proteins. Since the mechanism of amyloid disassembly by ATP-independent chaperones is unknown, we reconstructed atomic models of the amyloids self-assembled from TGFBIp-derived peptides and their complex with L-PGDS using cryo-EM and NMR. We show that L-PGDS specifically recognizes structurally frustrated regions in the amyloids and releases those frustrations. The released free energy increases the chaperone's binding affinity to amyloids, resulting in local restructuring and breakage of amyloids to protofibrils. Our mechanistic model provides insights into the alternative source of energy utilized by ATP-independent disaggregases and highlights the possibility of using these chaperones as treatment strategies for different types of amyloid-related diseases.
履歴
登録
2022年11月19日
登録サイト: PDBJ / 処理サイト: PDBJ
改定 1.0
2023年7月26日
Provider: repository / タイプ: Initial release
改定 1.1
2024年2月21日
Group: Data collection / Data processing / Source and taxonomy カテゴリ: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_3d_reconstruction / em_entity_assembly_naturalsource Item: _em_3d_reconstruction.num_particles / _em_entity_assembly_naturalsource.ncbi_tax_id / _em_entity_assembly_naturalsource.organism