6C3F

AMYLOID FORMING PEPTIDE IYKVEI FROM TRANSTHYRETIN

6C3F の概要

• エントリーDOI: 10.2210/pdb6c3f/pdb
• 分子名称: ILE-TYR-LYS-VAL-GLU-ILE, trifluoroacetic acid (3 entities in total)
• 機能のキーワード: amyloid, transthyretin, fibril, protein fibril
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 1643.88

構造登録者

Saelices, L.,Sawaya, M.R.,Eisenberg, D.S. (登録日: 2018-01-09, 公開日: 2018-04-18, 最終更新日: 2024-03-13)

主引用文献

Saelices, L.,Sievers, S.A.,Sawaya, M.R.,Eisenberg, D.S.
Crystal structures of amyloidogenic segments of human transthyretin.
Protein Sci., 27:1295-1303, 2018

PubMed Abstract: Amyloid diseases are characterized by the deposition of proteins in the form of amyloid fibrils, in organs that eventually fail. The development of effective drug candidates follows from the understanding of the molecular processes that lead to protein aggregation. Here, we study amyloidogenic segments of transthyretin (TTR). TTR is a transporter of thyroxine and retinol in the blood and cerebrospinal fluid. When mutated and/or as a result of aging, TTR aggregates into amyloid fibrils that accumulate in organs such as the heart. Recently, we reported two amyloidogenic segments that drive amyloid aggregation. Here, we report the crystal structure of another six amyloidogenic segments of TTR. We found that the segments from the C-terminal region of TTR form in-register steric-zippers with highly-interdigitated, wet interfaces, whereas the β-strand B from the N-terminal region of TTR forms an out-of-register assembly, previously associated with oligomeric formation. Our results contribute fundamental information for understanding the mechanism of aggregation of TTR.

PubMed: 29626847
DOI: 10.1002/pro.3420

実験手法

X-RAY DIFFRACTION (1.499 Å)