Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T

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 Å resolution structure of crystals containing overlapping tropomyosin N and C termini (TM-N and TM-C) and the 2.9 Å 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

Laparoscopic liver resection for liver metastasis of leiomyosarcoma of the thigh : a case report

Background Although there is no established treatment strategy for liver metastasis of leiomyosarcoma, liver resection has been reported to be effective in some cases. However, almost all liver resections performed for liver metastasis of primary leiomyosarcoma are reported to be open resections, and there are few reports of liver resection performed by laparoscopy. Here, we report a case of laparoscopic liver resection for liver metastasis of a leiomyosarcoma in the right thigh. Case presentation An 80-year-old man was diagnosed with leiomyosarcoma of the right thigh with liver metastasis. The primary tumor was first resected, and he was discharged on the 25th postoperative day. Four months after primary tumor resection, a laparoscopic right posterior sectionectomy was performed. There were no postoperative complications, and the patient was discharged on the 11th postoperative day with a histopathological diagnosis of liver metastasis of leiomyosarcoma and negative resection margins. Currently, 9 months have passed since the resection of the primary tumor, and 5 months have passed since the laparoscopic liver resection; there is no recurrence. Conclusions The liver metastasis of leiomyosarcoma was successfully removed, with good short-term outcomes after the laparoscopic liver resection. Laparoscopic liver resection seems to be effective for liver metastasis of leiomyosarcoma, which is characterized by a high recurrence rate after surgery. However, more case studies may be necessary to examine the effectiveness and long-term results of laparoscopic liver resection for the treatment of liver metastasis of leiomyosarcoma