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トップページ  »   2017年5月9日(火)14:40~16:10 FRIMS講演会「Exploring GPCR and membrane protein dynamics with solution NMR and X-ray free-electron lasers」ゲプハルト・シェトラー教授(スイス連邦工科大学、ポール・シェラー研究所)

  • 国立大学法人 名古屋工業大学
  • 特別演習スケジュール

2017年5月9日(火)14:40~16:10 FRIMS講演会「Exploring GPCR and membrane protein dynamics with solution NMR and X-ray free-electron lasers」ゲプハルト・シェトラー教授(スイス連邦工科大学、ポール・シェラー研究所)

ゲプハルト・シェトラー教授 (スイス連邦工科大学、ポール・シェラー研究所)による講演を開催しますので、博士前期学生、博士後期学生の皆様は奮ってご参加ください。

 

日時: 2017年5月9日(火)14:40-16:10
場所: 4号館1階・大ホール               

 

なお,本講演は博士前期・博士後期「特別演習」認定講義となりますので,出席の上,必要な条件を満たした場合は,以下の科目の認定要件に加算されます。


・材料・エネルギー特別演習1・2
・情報・社会特別演習1・2
・材料・エネルギー先進特別演習1・2
・情報・社会先進特別演習1・2

 

主催: フロンティア研究院 / 文科省「海外研究ユニット招聘」事業
担当教員: 神取 秀樹   教授   (しくみ領域/オプトバイオテクノロジー研究センター)

 

Exploring GPCR and membrane protein dynamics with solution NMR and X-ray free-electron lasers

 

Gebhard F.X. Schertler

 

Professor for Structural Biology ETH Zürich D-BIOL and

Head of Biology and Chemistry Division, Paul Scherrer Institute PSI, Switzerland

 

Our collaborative team has successfully introduced N15 -labeled valine in a conformationally stabilized beta 1 adrenergic receptor and used the labeled positions for evaluating backbone dynamics of this GPCR. We were able to see heterogeneous responses across the receptor after binding a number of agonists and antagonists. But, remarkably, we were able to pick up a homogenous response reflecting the signaling transmission within the receptor in a region distant from the ligand binding site. In addition, we were able to observe changes of loop dynamics in the ligand entrance channel of the adrenergic receptor. We were able to outline a detailed allosteric mechanism for GPCR activation. Free-electron lasers are X-ray sources with unprecedented peak brilliance. We are applying them to explore serial crystallography for membrane proteins. Using bacteriorhodopsin as a model system, we were able to trigger its photo cycle in lipidic cubic phase, and we have also observed reaction intermediates at room temperature. We can observe already after 16 ns disordering of a water cluster that is directly hydrogen bonded to the Schiff base. The difference densities are further increasing over time. This change is an important part of the mechanism that modulates the affinity of the proton to the Schiff base nitrogen. Later structural changes raise the pKa of Asp85 to the point where it spontaneously accepts a proton from the Schiff base. Using the exceptional free electron laser facilities at LCLS and SACLA, our consortium has measured a first molecular movie of structural changes in a membrane protein.

 

Membrane protein structural biology using X-ray free electron lasers

Current opinion in structural biology 33, 115-125 (2015)

A three-dimensional movie of structural changes in bacteriorhodopsin

Science 354 (6319), 1552-1557 (2016)

Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography

Nature Communications 7, 12314 (2016)

Lipidic cubic phase serial millisecond crystallography using synchrotron radiation

IUCrJ 2 (2), 168-176 (2015)

Molecular signatures of G-protein-coupled receptors

Nature 494 (7436), 185-194 (2013)

Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region

Nature 536 (7617), 484-487 (2016)

Probing G [alpha] i1 protein activation at single-amino acid resolution

Nature structural & molecular biology 22 (9), 686-694 (2015)

Backbone NMR reveals allosteric signal transduction networks in the β1-adrenergic receptor

Nature 530 (7589), 237-241 (2016)

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