The University of Tokyo · 생화학·유전·분자생물학
Chikashi Toyoshima 교수의 연구실은 주로 근육 내 세포소기관인 조직망에서 작용하는 칼슘 펌프(SERCA)의 구조 기반 기능 해석을 핵심으로 삼고 있습니다. 고해상도 X선 결정학과 냉동전자현미경을 활용해 칼슘 이온의 결합·해리 과정에서 발생하는 단백질의 기계적 변형과 인산화 작용의 역할을 체계적으로 규명하고 있습니다. 특히 인산화 조절 단백질인 프로스테인블란크(PLN)와의 상호작용 메커니즘 및 약물 결합 양상에 대한 원자 수준의 구조 분석도 진행 중입니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
The structures of the Ca2+-ATPase (SERCA1a) have been determined for five different states by X-ray crystallography. Detailed comparison of the structures in the Ca2+ bound form and unbound (but thapsigargin bound) form reveals that very large rearrangements of the transmembrane helices take place accompanying Ca2+ dissociation and binding and that they are mechanically linked with equally large movements of the cytoplasmic domains. The meanings of the rearrangements of the transmembrane helices
Long tubular vesicles have been grown from isolated Torpedo postsynaptic membranes, in which the receptors are arranged helically on the vesicle surface. The structures of these tubes have been analyzed by cryoelectron microscopy of specimens embedded in thin films of ice, combined with helical image reconstruction. Complete data sets from tubes belonging to several helical families have been obtained to a resolution of 17 A in all directions. Confirming a preliminary study (Toyoshima, C., and N
The inhibitory interaction of phospholamban (PLN) with the sarco(endo)plasmic reticulum Ca(2+) ATPase isoform 1 (SERCA1a) was modeled on the basis of several constraints which included (i) spontaneous formation of SS-bridges between mutants L321C in transmembrane helix 4 (M4) of SERCA1a and N27C in PLN and between V89C (M4) and V49C (PLN); (ii) definition of the face of the PLN transmembrane helix that interacts with SERCA; (iii) cross-linking between Lys-3 of PLN and Lys-397 and Lys-400 of SERC
Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum is the best-studied member of the P-type or E1/E2 type ion transporting ATPases. It has been crystallized in seven different states that cover nearly the entire reaction cycle. Here we describe the structure of this ATPase complexed with phosphate analogs BeF(3)(-) and AlF(4)(-) in the absence of Ca(2+), which correspond to the E2P ground state and E2 approximately P transition state, respectively. The luminal gate is open with BeF(3)(-) an
