8G2V

Cryo-EM structure of recombinant human LECT2 amyloid fibril core

8G2V の概要

• エントリーDOI: 10.2210/pdb8g2v/pdb
• EMDBエントリー: 29682
• 分子名称: Leukocyte cell-derived chemotaxin-2 (1 entity in total)
• 機能のキーワード: amyloid, lect2, human, recombinant, fibril, protein, alect2, cryo-em, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 23897.52

構造登録者

Richards, L.S.,Flores, M.D.,Zink, S.,Schibrowsky, N.A.,Sawaya, M.R.,Rodriguez, J.A. (登録日: 2023-02-06, 公開日: 2023-08-16, 最終更新日: 2023-11-15)

主引用文献

Richards, L.S.,Flores, M.D.,Zink, S.,Schibrowsky, N.A.,Sawaya, M.R.,Rodriguez, J.A.
Cryo-EM structure of a human LECT2 amyloid fibril reveals a network of polar ladders at its core.
Structure, 31:1386-1393.e3, 2023

PubMed Abstract: ALECT2 systemic amyloidosis is associated with deposition of the leukocyte cell-derived chemotaxin-2 (LECT2) protein in the form of fibrils. In ALECT2 amyloidosis, ALECT2 fibrils deposit in the glomerulus, resulting in renal failure. Patients lack effective treatment options outside of renal transplant or dialysis. The structure of globular LECT2 has been determined but structures of ALECT2 amyloid fibrils remain unknown. Using single-particle cryo-EM, we find that recombinant human LECT2 forms robust twisting fibrils with canonical amyloid features. ALECT2 fibrils contain two mating protofilaments spanning residues 55-75 of the LECT2 sequence. The geometry of the ALECT2 fibril displays features in line with other pathogenic amyloids. Its core is tightly packed and stabilized by both hydrophobic contacts and hydrogen-bonded uncharged polar residues. The robustness of ALECT2 fibril cores is illustrated by their resistance to denaturants and proteases. This ALECT2 fibril structure presents a potential new target for treatments against ALECT2 systemic amyloidosis.

PubMed: 37657439
DOI: 10.1016/j.str.2023.08.007

実験手法

ELECTRON MICROSCOPY (2.715 Å)