7N2Z

Crystal Structure of a de Novo Three-stranded Coiled Coil Peptide Containing Trigonal Pyrmidal Pb(II) complexes in the dual Tris-thiolate Site

7N2Z の概要

• エントリーDOI: 10.2210/pdb7n2z/pdb
• 分子名称: Pb(II)2-(GRAND CoilSerL16CL23C)3, ZINC ION, LEAD (II) ION, ... (5 entities in total)
• 機能のキーワード: three-stranded coiled coil, 3scc, trigonal pyramidal lead complexes, de novo protein, desinged protein, heavy metal sites in protein, biosynthetic protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4620.05

構造登録者

Ruckthong, L.,Stuckey, J.A.,Pecoraro, V.L. (登録日: 2021-05-30, 公開日: 2022-06-01, 最終更新日: 2023-10-18)

主引用文献

Pinter, T.B.J.,Ruckthong, L.,Stuckey, J.A.,Deb, A.,Penner-Hahn, J.E.,Pecoraro, V.L.
Open Reading Frame 1 Protein of the Human Long Interspersed Nuclear Element 1 Retrotransposon Binds Multiple Equivalents of Lead.
J.Am.Chem.Soc., 143:15271-15278, 2021

PubMed Abstract: The human long interspersed nuclear element 1 (LINE1) has been implicated in numerous diseases and has been suggested to play a significant role in genetic evolution. Open reading frame 1 protein (ORF1p) is one of the two proteins encoded in this self-replicating mobile genetic element, both of which are essential for retrotransposition. The structure of the three-stranded coiled-coil domain of ORF1p was recently solved and showed the presence of tris-cysteine layers in the interior of the coiled-coil that could function as metal binding sites. Here, we demonstrate that ORF1p binds Pb(II). We designed a model peptide, L16CL23C, to mimic two of the ORF1p Cys layers and crystallized the peptide both as the apo-form and in the presence of Pb(II). Structural comparison of the ORF1p with apo-(L16CL23C) shows very similar Cys layers, preorganized for Pb(II) binding. We propose that exposure to heavy metals, such as lead, could influence directly the structural parameters of ORF1p and thus impact the overall LINE1 retrotransposition frequency, directly relating heavy metal exposure to genetic modification.

PubMed: 34494819
DOI: 10.1021/jacs.1c06461

実験手法

X-RAY DIFFRACTION (1.29 Å)