7AHS

titin-N2A Ig81-Ig83

7AHS の概要

• エントリーDOI: 10.2210/pdb7ahs/pdb
• 分子名称: Isoform 5 of Titin, 1,2-ETHANEDIOL, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: titin, n2a, structural protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 128101.73

構造登録者

Fleming, J.R.,Mayans, O. (登録日: 2020-09-25, 公開日: 2021-03-24, 最終更新日: 2024-01-31)

主引用文献

Stronczek, C.,Lange, S.,Bullard, B.,Wolniak, S.,Borgeson, E.,Mayans, O.,Fleming, J.R.
The N2A region of titin has a unique structural configuration.
J.Gen.Physiol., 153:-, 2021

PubMed Abstract: The N2A segment of titin is a main signaling hub in the sarcomeric I-band that recruits various signaling factors and processing enzymes. It has also been proposed to play a role in force production through its Ca2+-regulated association with actin. However, the molecular basis by which N2A performs these functions selectively within the repetitive and extensive titin chain remains poorly understood. Here, we analyze the structure of N2A components and their association with F-actin. Specifically, we characterized the structure of its Ig domains by elucidating the atomic structure of the I81-I83 tandem using x-ray crystallography and computing a homology model for I80. Structural data revealed these domains to present heterogeneous and divergent Ig folds, where I81 and I83 have unique loop structures. Notably, the I81-I83 tandem has a distinct rotational chain arrangement that confers it a unique multi-domain topography. However, we could not identify specific Ca2+-binding sites in these Ig domains, nor evidence of the association of titin N2A components with F-actin in transfected C2C12 myoblasts or C2C12-derived myotubes. In addition, F-actin cosedimentation assays failed to reveal binding to N2A. We conclude that N2A has a unique architecture that predictably supports its selective recruitment of binding partners in signaling, but that its mechanical role through interaction with F-actin awaits validation.

PubMed: 33836065
DOI: 10.1085/jgp.202012766

実験手法

X-RAY DIFFRACTION (2.05 Å)