3CAE

Structure of NNQQNY as an insert in T7 endonuclease I

3CAE の概要

• エントリーDOI: 10.2210/pdb3cae/pdb
• 分子名称: Endonuclease I (2 entities in total)
• 機能のキーワード: t7 endonuclease i, amyloid, steric zipper, hydrolase
• 由来する生物種: Enterobacteria phage T7; 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 156508.29

構造登録者

Guo, Z.,Eisenberg, D. (登録日: 2008-02-19, 公開日: 2008-07-22, 最終更新日: 2023-08-30)

主引用文献

Guo, Z.,Eisenberg, D.
The structure of a fibril-forming sequence, NNQQNY, in the context of a globular fold.
Protein Sci., 17:1617-1623, 2008

PubMed Abstract: Numerous human disorders are associated with the formation of protein fibrils. The fibril-forming capacity of a protein has been found in recent studies to be determined by a short segment of residues that forms a dual beta-sheet, called a steric zipper, in the spine of the fibril. The question arises as to whether a fibril-forming segment, when inserted within the sequence of a globular protein, will invariably cause the protein to form fibrils. Here we investigate this question by inserting the known fibril-forming segment NNQQNY into the globular enzyme, T7 endonuclease I. From earlier studies, we know that in its fibril form, NNQQNY is in an extended conformation. We first found that the inserted NNQQNY stimulates fibril formation of T7 endonuclease I in solution. Thus NNQQNY within T7 endonuclease I can exist in an extended conformation, capable of forming the steric zipper in the core of a fibril. We also found that T7 endonuclease I folds into a decamer that does not form fibrils. We determined the structure of the decamer by X-ray crystallography, finding an unusual oligomer without point group symmetry, and finding that the NNQQNY segments within the decamer adopt two twisted conformations, neither is apparently able to fibrillize. We conclude that twisting of fibril forming sequences from the fully extended conformation, imposed by the context of their placement in proteins, can interfere with fibril formation.

PubMed: 18552127
DOI: 10.1110/ps.036368.108

実験手法

X-RAY DIFFRACTION (3 Å)