2Z5I

Crystal structure of the head-to-tail junction of tropomyosin

2Z5I の概要

• エントリーDOI: 10.2210/pdb2z5i/pdb
• 分子名称: General control protein GCN4 and Tropomyosin alpha-1 chain, Tropomyosin alpha-1 chain and General control protein GCN4, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: actin, troponin, tropomyosin, cytoskeleton, cardiomyopathy, contractile protein
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast, rabbit); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: P58772; Nucleus: P03069
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 57578.00

構造登録者

Murakami, K.,Nozawa, K.,Tomii, K.,Kudou, N.,Igarashi, N.,Shirakihara, Y.,Wakatsuki, S.,Stewart, M.,Yasunaga, T.,Wakabayashi, T. (登録日: 2007-07-12, 公開日: 2008-04-22, 最終更新日: 2024-03-13)

主引用文献

Murakami, K.,Stewart, M.,Nozawa, K.,Tomii, K.,Kudou, N.,Igarashi, N.,Shirakihara, Y.,Wakatsuki, S.,Yasunaga, T.,Wakabayashi, T.
Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T
Proc.Natl.Acad.Sci.USA, 105:7200-7205, 2008

PubMed Abstract: Head-to-tail polymerization of tropomyosin is crucial for its actin binding, function in actin filament assembly, and the regulation of actin-myosin contraction. Here, we describe the 2.1 A resolution structure of crystals containing overlapping tropomyosin N and C termini (TM-N and TM-C) and the 2.9 A resolution structure of crystals containing TM-N and TM-C together with a fragment of troponin-T (TnT). At each junction, the N-terminal helices of TM-N were splayed, with only one of them packing against TM-C. In the C-terminal region of TM-C, a crucial water in the coiled-coil core broke the local 2-fold symmetry and helps generate a kink on one helix. In the presence of a TnT fragment, the asymmetry in TM-C facilitates formation of a 4-helix bundle containing two TM-C chains and one chain each of TM-N and TnT. Mutating the residues that generate the asymmetry in TM-C caused a marked decrease in the affinity of troponin for actin-tropomyosin filaments. The highly conserved region of TnT, in which most cardiomyopathy mutations reside, is crucial for interacting with tropomyosin. The structure of the ternary complex also explains why the skeletal- and cardiac-muscle specific C-terminal region is required to bind TnT and why tropomyosin homodimers bind only a single TnT. On actin filaments, the head-to-tail junction can function as a molecular swivel to accommodate irregularities in the coiled-coil path between successive tropomyosins enabling each to interact equivalently with the actin helix.

PubMed: 18483193
DOI: 10.1073/pnas.0801950105

実験手法

X-RAY DIFFRACTION (2.1 Å)