• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Structural basis for an essential subunit interaction in influenza virus RNA polymerase PB1-PB2

Research Project

Project/Area Number 21370046
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionYokohama City University

Principal Investigator

PARK Sam-yong  横浜市立大学, 生命ナノシステム科学研究科, 教授 (20291932)

Co-Investigator(Kenkyū-buntansha) FUKUNISHI Yoshihumi  産業技術総合研究所, バイオメディシナル情報研究センター, 主任研究員 (60357895)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2010: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2009: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywordsインフルエンザ / RNAポリメラーゼ / 構造解析 / 創薬 / 複合体 / 構造我解析
Research Abstract

Influenza virus RNA-dependent RNA polymerase is a multi-functional heterotrimer, which uses a "cap-snatching" mechanism to produce viral mRNA. Host cell mRNA is cleaved to yield a cap-bearing oligonucleotide which can be extended using viral genomic RNA as a template. The cap binding and endonuclease activities are only activated once viral genomic RNA is bound. This requires signaling from the RNA-binding PB1 subunit to the cap-binding PB2 subunit, and the interface between these two subunits is essential for polymerase activity. We have defined this interaction surface by protein crystallography, and tested the effects of mutating contact residues on the function of the holo-enzyme. This novel interface is surprisingly small, yet it plays a crucial role in regulating the 250 kDa polymerase, and is completely conserved among avian and human influenza.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (48 results)

All 2011 2010 2009 Other

All Journal Article (20 results) (of which Peer Reviewed: 2 results) Presentation (24 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Oxygen binding and redox properties of the heme in soluble guanylate cyclase : Implications for the mechanism of ligand discrimination2011

    • Author(s)
      Makino R, Park SY, Obayashi E, Iizuka T, Hori H, Shiro Y.
    • Journal Title

      J Biol Chem

      Volume: 286(18) Pages: 15678-87

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Crystal structure of the human centromeric nucleosome containing CENP-A2011

    • Author(s)
      Tachiwana H, Kagawa W, Shiga T, Osakabe A, Miya Y, Saito K, Hayashi-Takanaka Y, Oda T, Sato M, Park SY, Kimura H, Kurumizaka H.
    • Journal Title

      Nature

      Volume: 476(7359) Pages: 232-5

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Structures and oxygen affinities of crystalline human hemoglobin C({beta} 6 Glu-> Lys) in the R and R2 quaternary structures2011

    • Author(s)
      Shibayama N, Sugiyama K, Park SY
    • Journal Title

      J Biol Chem

      Volume: 286(38) Pages: 33661-8

    • Related Report
      2011 Final Research Report
  • [Journal Article] Crystal Structures of Penicillin-Binding Proteins 4 and 5 from Haemophilus influenzae2010

    • Author(s)
      Kawai F, Clarke TB, Roper DI, Han GJ, Hwang KY, Unzai S, Obayashi E, Park SY, Tame JR
    • Journal Title

      J Mol Biol

      Volume: 396(3) Pages: 634-45

    • Related Report
      2011 Final Research Report
  • [Journal Article] Direct determination of protonation states of histidine residues in a 2 A neutron structure of deoxy-human normal adult hemoglobin and implications for the Bohr effect2010

    • Author(s)
      Kovalevsky AY, Chatake T, Shibayama N, Park SY, Ishikawa T, Mustyakimov M, Fisher Z, Langan P, Morimoto Y.
    • Journal Title

      J Mol Biol

      Volume: 398(2) Pages: 276-91

    • Related Report
      2011 Final Research Report
  • [Journal Article] Autotransporter passenger proteins : virulence factors with common structural themes2010

    • Author(s)
      Nishimura K, Tajima N, Yoon YH, Park SY, Tame JR
    • Journal Title

      J Mol Med

      Volume: 88(5) Pages: 451-8

    • Related Report
      2011 Final Research Report
  • [Journal Article] A novel intein-like autoproteolytic mechanism in autotransporter proteins2010

    • Author(s)
      Tajima N, Kawai F, Park SY, Tame JR
    • Journal Title

      J Mol Biol

      Volume: 402(4) Pages: 645-56

    • Related Report
      2011 Final Research Report
  • [Journal Article] Role of domains within the autotransporter Hbp/Tsh2010

    • Author(s)
      Nishimura K, Yoon YH, Kurihara A, Unzai S, Luirink J, Park SY, Tame JR
    • Journal Title

      Acta Crystallogr D Biol Crystallogr

      Volume: 66(12) Pages: 1295-300

    • Related Report
      2011 Final Research Report
  • [Journal Article] 新規抗インフルエンザウイルス薬の開発基盤となるRNAポリメラーゼの構造解析2010

    • Author(s)
      朴三用
    • Journal Title

      生物物理

      Volume: Vol.50, No.2 Pages: 74-79

    • NAID

      10025976244

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] タンパク質発現プロトコール2010

    • Author(s)
      浅賀正充、朴三用
    • Journal Title

      実験医学別冊(羊土社)

      Pages: 94-111

    • Related Report
      2011 Final Research Report
  • [Journal Article] インフルエザウスRNAポリメラーゼの構造解析と創薬研究2010

    • Author(s)
      杉山佳奈子、尾林栄治、吉田尚史、朴三用
    • Journal Title

      日本結晶学会

      Volume: 52 Pages: 271-278

    • Related Report
      2011 Final Research Report
  • [Journal Article] インフルエンザウイルスRNAポリメラーゼの構造解析と創薬研究2010

    • Author(s)
      杉山佳奈子、尾林栄治、吉田尚史、朴三用
    • Journal Title

      日本結晶学会

      Volume: 52 Pages: 271-278

    • NAID

      10027673105

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase2009

    • Author(s)
      Sugiyama K, Obayashi E, Kawaguchi A, Suzuki Y, Tame JR, Nagata K, Park SY.
    • Journal Title

      EMBO J

      Volume: 28(12) Pages: 1803-11

    • Related Report
      2011 Final Research Report
  • [Journal Article] Structural Studies of a Bacterial Condensin Complex Reveal ATP-Dependent Disruption of Intersubunit Interactions2009

    • Author(s)
      Woo JS, Lim JH, Shin HC, Suh MK, Ku B, Lee KH, Joo K, Robinson H, Lee J, Park SY, Ha NC, Oh BH.
    • Journal Title

      Cell

      Volume: 136(1) Pages: 85-96

    • Related Report
      2011 Final Research Report
  • [Journal Article] The nature of the TRAP-Anti-TRAP complex2009

    • Author(s)
      Watanabe M, Heddle JG, Kikuchi K, Unzai S, Akashi S, Park SY, Tame JR
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 106(7) Pages: 2176-81

    • Related Report
      2011 Final Research Report
  • [Journal Article] Visualizing breathing motion of internal cavities in concert with ligand migration in myoglobin2009

    • Author(s)
      Tomita A, Sato T, Ichiyanagi K, Nozawa S, Ichikawa H, Chollet M, Kawai F, Park SY, Tsuduki T, Yamato T, Koshihara SY, Adachi SI
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 106(8) Pages: 2612-6

    • Related Report
      2011 Final Research Report
  • [Journal Article] Mutational Analysis of the Substrate Specificity of Escherichia coli Penicillin Binding Protein 4(PBP4)2009

    • Author(s)
      Clarke T, Kawai F, Park SY, Tame J, Dowson C, Roper D.
    • Journal Title

      Biochemistry

      Volume: 48(12) Pages: 2675-83

    • Related Report
      2011 Final Research Report
  • [Journal Article] RNA and Protein Complexes of trp RNA-Binding Attenuation Protein Characterized by Mass Spectrometry2009

    • Author(s)
      Akashi S, Watanabe M, Heddle JG, Unzai S, Park SY, Tame JR
    • Journal Title

      Anal Chem

      Volume: 81(6) Pages: 2218-26

    • Related Report
      2011 Final Research Report
  • [Journal Article] 抗インフルエンザ薬の開発研究2009

    • Author(s)
      朴三用
    • Journal Title

      Bipphiliaビオフィリア(アドスリ社)

      Volume: 5(4) Pages: 25-29

    • Related Report
      2011 Final Research Report
  • [Journal Article] Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase2009

    • Author(s)
      Sugiyama K, Obayashi E, Kawaguchi A, Suzuki Y, Tame JR, Nagata K, Park SY
    • Journal Title

      EMBO J. 28(12)

      Pages: 286-92

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Structure of PB1-PB2 subunit interface of inflenza A virus RNA polymerase2011

    • Author(s)
      Sugiyama K, Obayashi E, Kawaguchi A, Suzuki Y, Tame JR, Nagata K, Park SY
    • Organizer
      IUCr
    • Place of Presentation
      Palacio Municipal de Congresos. Madrid, Spain
    • Related Report
      2011 Final Research Report
  • [Presentation] The structural basis for the essential PA-PB1 subunit interaction in influenza RNA polymerase2011

    • Author(s)
      Yoshida H, Obayashi E, Kawai F, Shibayama N, Kawaguchi A, Nagata K, Tame JR, Park SY
    • Organizer
      IUCr
    • Place of Presentation
      Palacio Municipal de Congresos. Madrid, Spain
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Studies of the Influenza RNA-polymerase for Novel Drug Design2011

    • Author(s)
      Sam-Yong Park
    • Organizer
      The 9^<th> International Symposium for Future Drug Design and Medical Care
    • Place of Presentation
      Hokkaido University
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Studies of the Influenza RNA-polymerase for Novel Drug Design2011

    • Author(s)
      Park SY
    • Organizer
      The 9^<th> International Symposium for Future Drug Design and Medical Care
    • Place of Presentation
      Hokkaido University(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規抗ウイルス薬の開発基盤となるRNAポリメラーゼの構造解析2010

    • Author(s)
      朴三用
    • Organizer
      平成22年度KASTフォーラム1ドイツバイオ交流フォーラム
    • Place of Presentation
      川崎
    • Year and Date
      2010-07-02
    • Related Report
      2011 Final Research Report
  • [Presentation] 新規抗インフルエンサウイルス薬の開発基盤となるRNAポリメラーゼの構造解析2010

    • Author(s)
      朴三用
    • Organizer
      第27回PFシンポジウム
    • Place of Presentation
      筑波
    • Related Report
      2011 Final Research Report
  • [Presentation] インフルエンザRNAポリメラーゼの構造解析2010

    • Author(s)
      朴三用
    • Organizer
      第47回日本蛋白質科学会
    • Place of Presentation
      北海道大学
    • Related Report
      2011 Final Research Report
  • [Presentation] インフルエンザウイルスのRNAポリメラーゼサブユニットPB1-PB2サブユニト間相互作用の解明2010

    • Author(s)
      杉山佳奈子、尾林栄治、川口敦史、鈴木由佳理、テイムジェレミー、永田恭介、朴三用
    • Organizer
      第10回日本蛋白質科学会年会
    • Place of Presentation
      札幌
    • Related Report
      2011 Final Research Report
  • [Presentation] インフルエンザウイルスのRNAポリメラーゼサブユニットPA-PB1サブユニト間相互作用の解明2010

    • Author(s)
      吉田尚史、尾林栄治、河合文啓、川口敦史、永田恭介、テイムジェレミー、朴三用
    • Organizer
      第10回日本蛋白質科学会年会
    • Place of Presentation
      札幌
    • Related Report
      2011 Final Research Report
  • [Presentation] 新規抗インフルエンザウイルス薬の開発基盤となるRNAポリメラーゼの構造解析2010

    • Author(s)
      朴三用
    • Organizer
      第34回阿蘇シンポジウム
    • Place of Presentation
      阿蘇
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Insight into the Subunit Contact of the Influenza Virus RNA Polymerase2010

    • Author(s)
      Sam-Yong Park
    • Organizer
      2^<nd> International Symposium on Drug Discovery and Design by NMR
    • Place of Presentation
      Yokohama City University
    • Related Report
      2011 Final Research Report
  • [Presentation] 新規抗ウイルス薬の開発基盤となるRNAポリメラーゼの構造解析2010

    • Author(s)
      朴三用
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Related Report
      2011 Final Research Report
  • [Presentation] インフルエンザRNAポリメラーゼの構造解析2010

    • Author(s)
      朴三用
    • Organizer
      第47回日本蛋白質科学会
    • Place of Presentation
      北海道大学(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] インフルエンザウイルスのRNAポリメラーゼサブユニットPB1-PB2サブユニット間相互作用の解明2010

    • Author(s)
      杉山佳奈子、尾林栄治、川口敦史、鈴木由佳理、テイム ジェレミー、永田恭介、朴三用
    • Organizer
      第47回日本蛋白質科学会
    • Place of Presentation
      北海道大学
    • Related Report
      2010 Annual Research Report
  • [Presentation] インフルエンザウイルスのRNAポリメラーゼサブユニットPA-PB1サブユニット間相互作用の解明2010

    • Author(s)
      吉田尚史、尾林栄治、河合文啓、川口敦史、永田恭介、テイム ジェレミー、朴三用
    • Organizer
      第47回日本蛋白質科学会
    • Place of Presentation
      北海道大学
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新規抗インフルエンザウイルス薬の開発基盤となるRNAポリメラーゼの構造解析2010

    • Author(s)
      朴三用
    • Organizer
      第34回 阿蘇シンポジウム
    • Place of Presentation
      阿蘇(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Structural Insight into the Subunit Contact of the Influenza Virus RNA Polymerase2010

    • Author(s)
      朴三用
    • Organizer
      2^<nd> International Symposium on Drug Discovery and Design by NMR
    • Place of Presentation
      Yokohama(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Structural Insight in to the Essential PA-PB1 Subunit Contact of the Influenza Virus RNA Polymerase2009

    • Author(s)
      Sam-Yong Park
    • Organizer
      VII European Symposium of the Protein Society
    • Place of Presentation
      Zurich, Switzerland
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Insight in to the Subunit Contact of the Influenza Virus RNA Polymerase2009

    • Author(s)
      Sam-Yong Park
    • Organizer
      America Crystallographic Association
    • Place of Presentation
      Toronto Canada
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Insight into the Subunit Contact of the Influenza Virus RNA Polymerase2009

    • Author(s)
      Sam-Yong Park
    • Organizer
      9th KIAS-SUN Structure and Function
    • Place of Presentation
      Seoul National University, Seoul, Korea
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Insight into the Essential Subunit Contact of the Influenza Virus RNA Polymerase2009

    • Author(s)
      E. Obayashi, K. Sugiyama, H. Yoshida, F. Kawai, A. Kawaguchi, Y. Suzuki, J. Tame, K. Nagata, SY Park
    • Organizer
      第47回日本生物物理学会
    • Place of Presentation
      徳島文理大学
    • Related Report
      2011 Final Research Report
  • [Presentation] Structure and function of Root effect fish hemoglobin2009

    • Author(s)
      S. Unzai, K. Imai, T. Yokoyama, SY Park, K. Nagai, J. Tame
    • Organizer
      第47回日本生物物理学会
    • Place of Presentation
      徳島文理大学
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Insight into the Subunit Contact of the Influenza Virus RNA Polymerase2009

    • Author(s)
      Sam-Yong Park
    • Organizer
      The 9th R. O. C-Japan Joint Seminar on Crystallography
    • Place of Presentation
      Osaka University
    • Related Report
      2011 Final Research Report
  • [Presentation] Structural Insight into the Subunit Contact of the Influenza Virus RNA Polymerase2009

    • Author(s)
      Sam-Yong Park
    • Organizer
      America Crystallographic Association
    • Place of Presentation
      Toronto Canada
    • Related Report
      2009 Annual Research Report
  • [Book] トピックス:万能インフルエンザ治療薬に道筋2009

    • Author(s)
      朴三用
    • Total Pages
      117
    • Publisher
      メディカル
    • Related Report
      2011 Final Research Report
  • [Book] メディカル・トピックス:万能インフルエンザ治療薬に道筋2009

    • Author(s)
      朴三用
    • Total Pages
      1
    • Publisher
      Newton 8月号
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.tsurumi.yokohama-cu.ac.jp/pdl/index.html

    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] インフルエンザウイルス由来のNAポリメラーゼ発現系構築と結晶化及び、抗インフルエンザ薬のスクリーニング方法2009

    • Inventor(s)
      朴三用、尾林栄治、永田恭介、川口敦史
    • Industrial Property Rights Holder
      公立大学法人横浜市立大学、国立大学法人筑波大学
    • Filing Date
      2009-07-02
    • Related Report
      2011 Final Research Report
    • Overseas

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi