9LIP

The cryo-EM structure of the native PMEL fibril lamella

9LIP の概要

• エントリーDOI: 10.2210/pdb9lip/pdb
• EMDBエントリー: 63119
• 分子名称: M-alpha, M-beta, ... (4 entities in total)
• 機能のキーワード: pmel, protein fibril
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 48
• 化学式量合計: 240667.60

構造登録者

Ma, B.Y.,Yao, Y.X.,Dong, H.,Li, D.,Liu, C. (登録日: 2025-01-14, 公開日: 2025-12-24)

主引用文献

Ma, B.,Yao, Y.,Dong, H.,Yang, L.,Li, D.,Zhao, Q.,Sun, B.,Chen, Y.,Liu, C.,Li, D.
Atomic structure and in situ visualization of native PMEL lamellae in melanosomes.
Nat Commun, 16:10300-10300, 2025

PubMed Abstract: Melanin synthesis within melanosomes critically depends on the fibrillar architecture formed by the pigment cell-specific protein PMEL. Although PMEL fibrils have historically been classified as functional amyloids, their native supramolecular organization in situ and detailed molecular architecture have remained unresolved. In this study, we combine in situ cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) to elucidate the native structural organization of PMEL fibrils within human melanosomes from both patient melanoma tissues and melanocyte cell lines. We demonstrate that PMEL does not form conventional isolated amyloid fibrils, but rather assembles into highly organized lamellar sheets consisting of laterally aligned fibrils interconnected by flexible linker regions. Cryo-EM structures reveal a distinctive butterfly-shaped fibril unit composed of multiple structured domains, including both the proteolytically cleaved Mα and Mβ fragments of PMEL, which assemble into a amyloid-like β-sheet arrangement. Notably, we identify intrinsically disordered regions critical for lamellar assembly and curvature and verify key glycosylation modifications in the structure. This architecture distinguishes PMEL fibrils from canonical amyloids and elucidates the molecular basis underlying melanosome integrity and pigmentation. Moreover, our work provides molecular insights relevant for pigmentation disorders and PMEL-associated diseases, including melanoma.

PubMed: 41271718
DOI: 10.1038/s41467-025-65221-0

実験手法

ELECTRON MICROSCOPY (3.48 Å)