8G2V
Cryo-EM structure of recombinant human LECT2 amyloid fibril core
Summary for 8G2V
| Entry DOI | 10.2210/pdb8g2v/pdb |
| EMDB information | 29682 |
| Descriptor | Leukocyte cell-derived chemotaxin-2 (1 entity in total) |
| Functional Keywords | amyloid, lect2, human, recombinant, fibril, protein, alect2, cryo-em, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 10 |
| Total formula weight | 23897.52 |
| Authors | Richards, L.S.,Flores, M.D.,Zink, S.,Schibrowsky, N.A.,Sawaya, M.R.,Rodriguez, J.A. (deposition date: 2023-02-06, release date: 2023-08-16, Last modification date: 2023-11-15) |
| Primary citation | 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 Cited by 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: 37657439DOI: 10.1016/j.str.2023.08.007 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.715 Å) |
Structure validation
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