2Z5H

Crystal structure of the head-to-tail junction of tropomyosin complexed with a fragment of TnT

Summary for 2Z5H

• Entry DOI: 10.2210/pdb2z5h/pdb
• Descriptor: General control protein GCN4 and Tropomyosin alpha-1 chain, Tropomyosin alpha-1 chain and General control protein GCN4, Troponin T, fast skeletal muscle isoforms, ... (4 entities in total)
• Functional Keywords: actin, troponin, tropomyosin, cytoskeleton, cardiomyopathy, four-helix bundle, contractile protein
• Biological source: Saccharomyces cerevisiae (baker's yeast, rabbit); More
• Cellular location: Cytoplasm, cytoskeleton: P58772; Nucleus: P03069
• Total number of polymer chains: 10
• Total formula weight: 59657.50

Authors

Murakami, K.,Nozawa, K.,Tomii, K.,Kudou, N.,Igarashi, N.,Shirakihara, Y.,Wakatsuki, S.,Stewart, M.,Yasunaga, T.,Wakabayashi, T. (deposition date: 2007-07-12, release date: 2008-04-22, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.89 Å)