3PPD

GGVLVN segment from Human Prostatic Acid Phosphatase Residues 260-265, involved in Semen-Derived Enhancer of Viral Infection

3PPD の概要

• エントリーDOI: 10.2210/pdb3ppd/pdb
• 分子名称: GGVLVN peptide, amyloid forming segment, ZINC ION, ACETIC ACID, ... (4 entities in total)
• 機能のキーワード: amyloid-like protofibril, amyloid fibrils, protein fibril
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 1: Secreted (By similarity). Isoform 2: Lysosome membrane; Single-pass type I membrane protein: P15309
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 683.10

構造登録者

Zhao, A.,Sawaya, M.R.,Eisenberg, D. (登録日: 2010-11-24, 公開日: 2011-06-29, 最終更新日: 2024-02-21)

主引用文献

Sievers, S.A.,Karanicolas, J.,Chang, H.W.,Zhao, A.,Jiang, L.,Zirafi, O.,Stevens, J.T.,Munch, J.,Baker, D.,Eisenberg, D.
Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation.
Nature, 475:96-100, 2011

PubMed Abstract: Many globular and natively disordered proteins can convert into amyloid fibrils. These fibrils are associated with numerous pathologies as well as with normal cellular functions, and frequently form during protein denaturation. Inhibitors of pathological amyloid fibril formation could be useful in the development of therapeutics, provided that the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibrils as templates, we have designed and characterized an all-D-amino-acid inhibitor of the fibril formation of the tau protein associated with Alzheimer's disease, and a non-natural L-amino-acid inhibitor of an amyloid fibril that enhances sexual transmission of human immunodeficiency virus. Our results indicate that peptides from structure-based designs can disrupt the fibril formation of full-length proteins, including those, such as tau protein, that lack fully ordered native structures. Because the inhibiting peptides have been designed on structures of dual-β-sheet 'steric zippers', the successful inhibition of amyloid fibril formation strengthens the hypothesis that amyloid spines contain steric zippers.

PubMed: 21677644
DOI: 10.1038/nature10154

実験手法

X-RAY DIFFRACTION (1.5 Å)