教員情報 - 横山　謙

■ 研究概要

生命の維持にはエネルギーが必要です。生命がエネルギー作り出す仕組みを研究するのが、生体エネルギー学(Bioenergetics) です。生命のエネルギー通貨である ATP の大部分は、ミトコンドリアでの呼吸による酸化的リン酸化により効率よく作られます。細胞内のATPは一定のレベルに保たれていますが、アポトーシスなどの重大なイベントが細胞に起こると、ATPチャンネルが開き、このことで細胞内のATPレベルは急速に低下します。細胞外に放出されたATPおよびその代謝産物は、ATP受容体に感知され、様々な生理現象が引き起こされます。このように、ATPはエネルギー通貨としての役割に加えて、シグナル伝達にも関与することがわかっています。私達は、ATP動態に関わる膜タンパク質の構造・機能を、クライオ電子顕微鏡による構造生物学により明らかにしていきます。ATPを作ることに加え、使う、通す膜タンパク質が研究対象になります。 ATP動態を支える膜タンパク質は、我々が生きていく上で必要不可欠なものであり、これらの膜タンパク質の働きを変える化合物は、重要な薬剤になる可能性があります。たとえば、ATPを使って細胞外を酸性化する V-ATPaseは、がん細胞の生存に必要とされ、その働きを抑える薬剤は、有力な抗がん剤になる可能性があります。クライオ電子顕微鏡でATP動態に関わる膜タンパク質の構造を解明し、病気の治療や健康維持に役立つ薬剤の開発につながる成果を得るべく研究を進めています。

■ 学会発表

1.	2018/09/28	Structure and Mechanism of V type ATP synthase from Thermus thermophilus.（International Symposium “50th anniversary of Thermus thermophilus discovery”）
2.	2018/09/25	Cryo EM structure of V type ATP synthase from Thermus thermophilus.（日本生化学会大会）
3.	2018/09/20	クライオ電顕による V型 ATP合成酵素の構造解析（第79回応用物理学会秋季学術講演会）
4.	2018/09/15	Structural analysis of membrane protein complex by cryoEM.（第56回日本生物物理学会年会）
5.	2014	Molecular basis of ADP-inhibition of V type ATPase/synthase（European Bioenergetics Conference）
6.	2014	Molecular basis of ADP-inhibition of V type ATPase/synthase（2014 ATPase symposium）
7.	2014	The ingenious structure of central rotor apparatus in VoV1; torque transmission mechanism in the central rotor of VoV1（日本生物物理学会年会）
8.	2014	V1 と Vo 間の回転力の伝わり方（分子モーター討論会）
9.	2013	岸川淳一, 横山謙: V型回転分子モーターの合成型と分解型をわける分子基盤（第三回分子モーター討論会, 東大,）
10.	2012	Reconstitution of Vacuolar type rotary H+-ATPase/synthase from Thermus thermophilus.（The 17th European Bioenergetic conference）
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■ 著書・論文歴

1.	2024/11	論文	Human F-ATP synthase as a drug target Pharmacological Research 209,107423-107423頁
2.	2023/07	論文	Mechanism of ATP hydrolysis dependent rotation of bacterial ATP synthase. Nature communications 14(1),pp.4090-4090
3.	2023/07	その他	タンパク質の構造解析手法とIn silicoスクリーニングへの応用事例
4.	2023/01	論文	Cryo-EM analysis of V/A-ATPase intermediates reveals the transition of the ground-state structure to steady-state structures by sequential ATP binding. The Journal of biological chemistry pp.102884-102884
5.	2022/10	その他	Structural transition of the ground-state structure to steady-state structures by sequential binding of ATP to V/A-ATPase
6.	2022/08	論文	Structural basis of unisite catalysis of bacterial F0F1-ATPase PNAS Nexus 1(3)
7.	2022/07	論文	Structures of Multisubunit Membrane Complexes With the CRYO ARM 200. Microscopy (Oxford, England) 71(5),pp.249-261
8.	2018/12/01	論文	Cryo em structure of intact rotary H+-ATPase/synthase from Thermus thermophilus Nature Communications 9(1),pp.89
9.	2018/01/01	論文	General anesthetics cause mitochondrial dysfunction and reduction of intracellular ATP levels PLoS ONE 13(1),pp.e0190213
10.	2016/10	論文	Rotation of artificial rotor axles in rotary molecular motors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113(40),pp.11214-11219
11.	2015/09/01	論文	GraDeR: Membrane Protein Complex Preparation for Single-Particle Cryo-EM. Structure (London, England : 1993) 23(9),pp.1769-1775
12.	2015/03	論文	The Ingenious Structure of Central Rotor Apparatus in VoV1; Key for Both Complex Disassembly and Energy Coupling between V-1 and V-o PLOS ONE 10(3),pp.e0119602
13.	2014/09	論文	F-subunit reinforces torque generation in V-ATPase EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS 43(8-9),pp.415-422
14.	2014/01	論文	Molecular Basis of ADP Inhibition of Vacuolar (V)-type ATPase/Synthase JOURNAL OF BIOLOGICAL CHEMISTRY 289(1),pp.403-412
15.	2013/08	論文	In Vivo Fluorescent Adenosine 5'-Triphosphate (ATP) Imaging of Drosophila melanogaster and Caenorhabditis elegans by Using a Genetically Encoded Fluorescent ATP Biosensor Optimized for Low Temperatures ANALYTICAL CHEMISTRY 85(16),pp.7889-7896
16.	2013/08	論文	Visualization of two distinct states of disassembly in the bacterial V-ATPase from Thermus thermophilus MICROSCOPY 62(4),pp.467-474
17.	2013/05	論文	Common Evolutionary Origin for the Rotor Domain of Rotary Atpases and Flagellar Protein Export Apparatus PLOS ONE 8(5),pp.e64695
18.	2013/01	論文	Mechanical Modulation of ATP-binding Affinity of V-1-ATPase JOURNAL OF BIOLOGICAL CHEMISTRY 288(1),pp.619-623
19.	2013	その他	膜タンパク質構造研究
20.	2012/08	論文	Single-molecule Analysis of Inhibitory Pausing States of V-1-ATPase JOURNAL OF BIOLOGICAL CHEMISTRY 287(34),pp.28327-28335
21.	2012/07	論文	Reconstitution of Vacuolar-type Rotary H+-ATPase/Synthase from Thermus thermophilus JOURNAL OF BIOLOGICAL CHEMISTRY 287(29),pp.24597-24603
22.	2012/01	論文	MRT letter: Expression of ATP sensor protein in Caenorhabditis elegans MICROSCOPY RESEARCH AND TECHNIQUE 75(1),pp.15-19
23.	2011/03	論文	Resolving stepping rotation in Thermus thermophilus H+-ATPase/synthase with an essentially drag-free probe NATURE COMMUNICATIONS 2,pp.233
24.	2009/12	論文	Crystal structure of A(3)B(3) complex of V-ATPase from Thermus thermophilus EMBO JOURNAL 28(23),pp.3771-3779
25.	2009/02	論文	Cryo-EM Structure of the Native GroEL-GroES Complex from Thermus thermophilus Encapsulating Substrate Inside the Cavity STRUCTURE 17(2),pp.287-293
26.	2009/02	論文	Mechanism of Inhibition of the V-Type Molecular Motor by Tributyltin Chloride BIOPHYSICAL JOURNAL 96(3),pp.1210-1217
27.	2008/07	論文	ATP hydrolysis and synthesis of a rotary motor V-ATPase from Thermus thermophilus JOURNAL OF BIOLOGICAL CHEMISTRY 283(30),pp.20789-20796
28.	2008/07	論文	Molecular mechanism of energy conservation in polysulfide respiration Nature Structural and Molecular Biology 15(7),pp.730-737
29.	2007/12	論文	Dodecamer rotor ring defines H+/ATP ratio for ATP synthesis of prokaryotic V-ATPase from Thermus thermophilus PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 104(51),pp.20256-20261
30.	2007/05	その他	[Two rotary molecular motors, V-ATPase and F0F1]. Seikagaku. The Journal of Japanese Biochemical Society 79(5),425-437頁
31.	2007/04	その他	[Unveiled multifunctionality of V-ATPase and the molecular mechanism revealed by X-ray crystal structures]. Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 52(4),335-341頁
32.	2007	その他	非侵襲.可視化技術ハンドブックーナノ・バイオ医療から情報システムまでー
33.	2006/12	論文	Reconstitution in vitro of V-1 complex of Thermus thermophilus V-ATPase revealed that ATP binding to the A subunit is crucial for V-1 formation JOURNAL OF BIOLOGICAL CHEMISTRY 281(50),pp.38582-38591
34.	2006/02	論文	Two-dimensional crystallization and analysis of projection images of intact Thermus thermophilus V-ATPase JOURNAL OF STRUCTURAL BIOLOGY 153(2),pp.200-206
35.	2006/01	論文	Leu(309) plays a critical role in the encapsulation of substrate protein into the internal cavity of GroEL JOURNAL OF BIOLOGICAL CHEMISTRY 281(2),pp.962-967
36.	2005/12	論文	Rotation scheme of V-1-motor is different from that of F-1-motor PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 102(50),pp.17929-17933
37.	2005/12	論文	Rotation, structure, and classification of prokaryotic V-ATPase JOURNAL OF BIOENERGETICS AND BIOMEMBRANES 37(6),pp.405-410
38.	2005/11	論文	Structure of a central stalk subunit F of prokaryotic V-type ATPase/synthase from Thermus thermophilus EMBO JOURNAL 24(22),pp.3974-3983
39.	2004/09	その他	[The sophisticated proton pump, V-type ATPase]. Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 49(12),2035-2043頁
40.	2004/08	その他	Crystal structure of the native chaperonin complex from Thermus thermophilus revealed unexpected asymmetry at the cis-cavity. Structure (London, England : 1993) 12(8),1471-1480頁
41.	2004/04	論文	The F subunit of Thermus thermophilus V-1-ATPase promotes ATPase activity but is not necessary for rotation JOURNAL OF BIOLOGICAL CHEMISTRY 279(17),pp.18085-18090
42.	2004/01	論文	Crystal structure of a central stalk subunit C and reversible association/dissociation of vacuole-type ATPase PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 101(1),pp.59-64
43.	2003/10	論文	Subunit arrangement in V-ATPase from Thermus thermophilus JOURNAL OF BIOLOGICAL CHEMISTRY 278(43),pp.42686-42691
44.	2003/09	論文	Crystallization of the chaperonin GroEL-GroES complex from Thermus thermophilus HB8 ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY 59(Pt 9),pp.1632-1634
45.	2003/07	論文	Rotation of the proteolipid ring in the V-ATPase JOURNAL OF BIOLOGICAL CHEMISTRY 278(27),pp.24255-24258
46.	2003/06/01	論文	Different roles of proteolipids and 70-kDa subunits of V-ATPase in growth and death of cultured human cells Genes to Cells 8(6),501-513頁
47.	2003/03	論文	Evidence for rotation of V-1-ATPase PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 100(5),pp.2312-2315
48.	2002/04	論文	Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75 FEBS LETTERS 516(1-3),pp.53-57
49.	2000/05/05	論文	V-type H+-ATPase/synthase from a thermophilic eubacterium, Thermus thermophilus. Subunit structure and operon Journal of Biological Chemistry 275(18),pp.13955-13961
50.	2000	その他	V-type H⁺ATPase/synthase from a thermophilic eubacterium, Thermus thermophilus THE JOURNAL OF BIOLOGICAL CHEMISTRY 275/18,13955-13961
51.	2000	その他	V-type H⁺ATPase/synthase from a thermophilic eubacterium, Thermus thermophilus
52.	1999/05	論文	-Activated lansoprazole inhibits cancer cell adhesion to extracellular matrix components. S. Intern. J. Oncol. 359,pp.53-55
53.	1999/05	その他	18. Gene cloning and overexpression of a geranylgeranyl diphosphate synthase of an extremely thermophilic bacterium, Thermus thermophilus. Biosci.Biothechnol.Biochem. 359,pp.53-55
54.	1999	その他	Gene cloning and overexpression of a geranylgeranyl diphosphate synthase of an extremely thermophilic bacterium, Thermus thermophilus Biosci. Biotechnol. Biochem. 63/,261-270
55.	1999	その他	Gene cloning and overexpression of a geranylgeranyl diphosphate synthase of an extremely thermophilic bacterium, Thermus thermophilus
56.	1998/11	論文	V-ATPase from Thermus thermophilus is inactivated during ATP hydrolysis but can synthesis ATP. The Journal of Biological Chemistry 273,pp.12248-12252
57.	1998/08	論文	-Prodigiosins uncouple mitochondrial and bacterial F-ATPases: evidence for their H+/Cl- symport activity. J. Biochem. 124,pp.547-556
58.	1998	その他	V-ATPase of Thermusthermophilus in Inactivated during ATP hydrolysis but can synthesis ATP The Journal of Biological Chemistry 237/32,20504
59.	1998	その他	V-ATPase of Thermusthermophilus in Inactivated during ATP hydrolysis but can synthesis ATP
60.	1994/10	論文	Isolation of prokaryotic VoV1-ATPase from a thermophilic eubacterium Thermus thermophilus. The Journal of Biological Chemistry 269,pp.12248-12253
61.	1994	その他	Isolation of prokaryotic V₀V₁-ATPase from a thermophilic eubacterium Thermus thermophilus J. Biol. Chem. 269/,12248
62.	1994	その他	Isolation of prokaryotic V₀V₁-ATPase from a thermophilic eubacterium Thermus thermophilus
63.	1993/06	論文	The TF1-ATPase and ATPase activities of assembled  and  complexes are stimulated by low and inhibited by high concentrations of rhodamine 6G whereas the dye only inhibits the , and complexes. J-Bioenerg-Biomembr. 25,pp.679-684
64.	1993	その他	The TF₁-ATPase and ATPase activities of assembled α₃β₃γ, α₃β₃γδ, α₃β₃γe complexes are stimulated by low and inhibited by high concentrations of rhodamine 6G J. Bioenerg. Biomembr. 25/,679
65.	1993	その他	The TF₁-ATPase and ATPase activities of assembled α₃β₃γ, α₃β₃γδ, α₃β₃γe complexes are stimulated by low and inhibited by high concentrations of rhodamine 6G
66.	1993	その他	Thermostable farnesyl diphosphate synthase of Bacillus stearothermophilus J. Biochem. 113/,355
67.	1993	その他	Thermostable farnesyl diphosphate synthase of Bacillus stearothermophilus
68.	1992/02	論文	Single site hydrolysis of 2',3'-O-(2,4,6-trinitrophenyl)-ATP by the F1-ATPase from thermophilic bacterium PS3 is accelerated by the chase-addition of excess ATP. The Journal of Biological Chemistry 267,pp.4551-4555
69.	1992	その他	Single site hydrolysis of 2', 3'-0-(2, 4, 6-trinitrophenyl)-ATP by the F1-ATPase from thermophilic bacterium PS3 is accelerated by the chase-addition of excess ATP J. Biol. Chem. 267/,4551
70.	1992	その他	Single site hydrolysis of 2', 3'-0-(2, 4, 6-trinitrophenyl)-ATP by the F1-ATPase from thermophilic bacterium PS3 is accelerated by the chase-addition of excess ATP
71.	1991	論文	Purification by dye-ligand chromatography and a crystallization study of the F1-ATPase and its major subunits, β and α, from a thermophilic bacterium, PS3 Journal of Biochemistry 109(3),pp.466-471
72.	1991	その他	Molecular cloning of genes encoding major two subunits of a eubacterial V-type ATPase from Thermus thermophilus Biochim Biophys Acta 1098/,13
73.	1991	その他	Molecular cloning of genes encoding major two subunits of a eubacterial V-type ATPase from Thermus thermophilus
74.	1991	その他	Purification by dye-ligand chromatography and a crystallization study of the F₁-ATPase and its major subunits, beta and alpha, from a thermophilic bacterium, PS3 J. Biochem. 109/,466
75.	1991	その他	Purification by dye-ligand chromatography and a crystallization study of the F₁-ATPase and its major subunits, beta and alpha, from a thermophilic bacterium, PS3
76.	1990/10/01	論文	Electron microscopy of the reconstituted complexes of the F1-ATPase with various subunit constitution revealed the location of the γ subunit in the central cavity of the molecule FEBS Letters 271(1-2),pp.111-115
77.	1990	論文	Thermus thermophilus membrane-associated ATPase. Indication of a eubacterial V-type ATPase Journal of Biological Chemistry 265(35),pp.21946-21950
78.	1990	その他	Electron microscopy of the reconstituted complexes of the F1-ATPase with various subunit constituted revealed the location of the gamma subunit in the central cavity of the molecule FEBS Lett. 271/,111
79.	1990	その他	Electron microscopy of the reconstituted complexes of the F1-ATPase with various subunit constituted revealed the location of the gamma subunit in the central cavity of the molecule
80.	1990	その他	Thermus thermophilus membrane-associated ATPase Indication of a eubacterial V-type ATPase
81.	1989	論文	The reconstituted α3 β3 δ complex of the thermostable F1-ATPase J. Biol. Chem. 264/,21837,pp.21837
82.	1989	論文	The reconstituted α3β3δ complex of the thermostable F1-ATPase Journal of Biological Chemistry 264(36),pp.21837-21841
83.	1989	その他	The reconstituted α3 β3 δ complex of the thermostable F1-ATPase
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■ 職歴

1.		金沢大学薬学部助手
2.		科学振興機構 ERATO-ICORP project GL
3.		京都産業大学総合生命科学部教授

■ 主要学科目

化学通論A

■ 所属学会

1.		日本分子生物学会
2.		日本生化学会
3.		日本生物物理学会

■ 研究課題・受託研究・科研費

1.		Study of H<sup>+</sup>-ATPase
2.	2020/04～2023/03	クライオ電子顕微鏡による V型ATPaseの回転機構の解明基盤研究(B)

■ 委員会・協会等

1.	～	日本生体エネルギー研究会常任幹事
2.		科学研究補助金審査員

■ ホームページ

http://www.cc.kyoto-su.ac.jp/~yokoken/index-j.htm

■ 現在の専門分野

構造生物化学, 細胞生物学, 機能生物化学, 生物物理学, 細胞生物学, 構造生物化学, 機能生物化学, 生物物理学, 構造生物化学　（キーワード：情報伝達,V-ATPaseの分子機構、生体エネルギー、老化、CryoEM、ATP、生体エネルギー、V-ATPase、CryoEM、ATP、生体エネルギー、V-ATPase）

■ 担当経験のある科目

1.	先端生命科学実習I（京都産業大学）
2.	先端生命科学演習２（京都産業大学生命科学部）
3.	先端生命科学演習２（京都産業大学生命科学部）
4.	先端生命科学英語１（京都産業大学生命科学部）
5.	先端生命科学英語１（京都産業大学生命科学部）

■ 外部研究者ID

orcID

0000-0002-6813-1096