Gas slow conformational transition upon GTP binding and a novel Gas regulator

被引:7
|
作者
Ahn, Donghoon [1 ]
Provasi, Davide [2 ]
Duc, Nguyen Minh [1 ,7 ]
Xu, Jun [3 ]
Salas-Estrada, Leslie [2 ]
Spasic, Aleksandar
Yun, Min Woo [1 ]
Kang, Juyeong [1 ,4 ]
Gim, Dongmin [1 ,4 ]
Lee, Jaecheol [1 ,5 ]
Du, Yang [6 ]
Filizola, Marta [2 ]
Chung, Ka Young [1 ]
机构
[1] Sungkyunkwan Univ, Sch Pharm, Suwon 16419, South Korea
[2] Icahn Sch Med Mt Sinai, Dept Pharmacol Sci, New York, NY 10029 USA
[3] Stanford Univ, Sch Med, Mol & Cellular Physiol, Stanford, CA 94305 USA
[4] Sungkyunkwan Univ, Dept Biopharmaceut Convergence, Suwon 16419, South Korea
[5] Sungkyunkwan Univ, Biomed Inst Convergence SKKU BICS, Suwon 16419, South Korea
[6] Chinese Univ Hong Kong, Kobilka Inst Innovat Drug Discovery, Sch Life & Hlth Sci, Shenzhen 518172, Guangdong, Peoples R China
[7] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden
基金
新加坡国家研究基金会; 美国国家卫生研究院;
关键词
MOLECULAR-DYNAMICS SIMULATIONS; HETEROTRIMERIC G-PROTEINS; CRYO-EM STRUCTURE; CRYSTAL-STRUCTURE; ADENYLYL-CYCLASE; STRUCTURAL DIVERSITY; MAXIMUM-ENTROPY; FORCE-FIELD; STATE; EXCHANGE;
D O I
10.1016/j.isci.2023.106603
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
G proteins are major signaling partners for G protein-coupled receptors (GPCRs). Although stepwise structural changes during GPCR-G protein complex formation and guanosine diphosphate (GDP) release have been reported, no information is available with regard to guanosine triphosphate (GTP) binding. Here, we used a novel Bayesian integrative modeling framework that combines data from hydrogendeuterium exchange mass spectrometry, tryptophan-induced fluorescence quenching, and metadynamics simulations to derive a ki-netic model and atomic-level characterization of stepwise conformational changes incurred by the beta(2)-adrenergic receptor (beta(2)AR)-Gs complex after GDP release and GTP binding. Our data suggest rapid GTP binding and GTP-induced dissociation of Gas from beta(2)AR and G(beta gamma), as opposed to a slow closing of the G(alpha s) alpha-helical domain (AHD). Yeast-two-hybrid screening using G(alpha s) AHD as bait identified melanoma-associated antigen D2 (MAGE D2) as a novel AHD-binding protein, which was also shown to accelerate the GTP-induced closing of the G(alpha s) AHD.
引用
收藏
页数:29
相关论文
共 50 条
  • [21] THE THYROID-HORMONE RECEPTOR INDUCES A CONFORMATIONAL CHANGE IN DNA UPON BINDING TO A NOVEL RECOGNITION SEQUENCE
    KING, IN
    LAVIN, T
    CLINICAL RESEARCH, 1990, 38 (01): : A98 - A98
  • [22] Distinct Conformational Transition Patterns of Noncoding 7SK snRNA and HIV TAR RNAs upon Tat Binding
    Lu, Jia
    Wong, Vivian
    Zhang, Yi
    Trung Tran
    Zhao, Liang
    Xia, Amy
    Xia, Tianbing
    Qi, Xin
    BIOCHEMISTRY, 2014, 53 (04) : 675 - 681
  • [23] CONFORMATIONAL TRANSITION OF THYROID-HORMONE RECEPTOR UPON HORMONE BINDING - DEMONSTRATION BY AQUEOUS 2-PHASE PARTITIONING
    ICHIKAWA, K
    HASHIZUME, K
    MIYAMOTO, T
    NISHII, Y
    YAMAUCHI, K
    OHTSUKA, H
    YAMADA, T
    JOURNAL OF ENDOCRINOLOGY, 1988, 119 (03) : 431 - 437
  • [24] EVIDENCE THAT CONFORMATIONAL-CHANGES UPON THE TRANSITION OF THE NATIVE TO THE MODIFIED FORM OF VITRONECTIN ARE NOT LIMITED TO THE HEPARIN-BINDING DOMAIN
    SEIFFERT, D
    FEBS LETTERS, 1995, 368 (01) : 155 - 159
  • [25] Novel DNA binding domain and genetic regulation model of Bacillus subtilis transition state regulator AbrB
    Vaughn, JL
    Feher, V
    Naylor, S
    Strauch, MA
    Cavanagh, J
    NATURE STRUCTURAL BIOLOGY, 2000, 7 (12) : 1139 - 1146
  • [26] Novel DNA binding domain and genetic regulation model of Bacillus subtilis transition state regulator AbrB
    Jeffrey L. Vaughn
    Victoria Feher
    Stephen Naylor
    Mark A. Strauch
    John Cavanagh
    Nature Structural Biology, 2000, 7 : 1139 - 1146
  • [27] Electronic Stopping of Slow Protons in Transition and Rare Earth Metals: Breakdown of the Free Electron Gas Concept
    Roth, D.
    Bruckner, B.
    Moro, M. V.
    Gruber, S.
    Goebl, D.
    Juaristi, J. I.
    Alducin, M.
    Steinberger, R.
    Duchoslav, J.
    Primetzhofer, D.
    Bauer, P.
    PHYSICAL REVIEW LETTERS, 2017, 118 (10)
  • [28] Slow Mass Transport and Statistical Evolution of an Atomic Gas across the Superfluid-Mott-Insulator Transition
    Hung, Chen-Lung
    Zhang, Xibo
    Gemelke, Nathan
    Chin, Cheng
    PHYSICAL REVIEW LETTERS, 2010, 104 (16)
  • [29] Novel Fiber Optic Gas Sensor Based on Photonic Crystal Slow-Light Waveguide
    Wang, Qi
    Han, Bo
    Wu, Di
    Zhao, Yong
    MICROWAVE AND OPTICAL TECHNOLOGY LETTERS, 2013, 55 (08) : 1796 - 1800
  • [30] Fundamental peak disappears upon binding of a noble gas: a case of the vibrational spectrum of PtCO in an argon matrix
    Ono, Yuriko
    Yagi, Kiyoshi
    Takayanagi, Toshiyuki
    Taketsugu, Tetsuya
    PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 2018, 20 (05) : 3296 - 3302