Direct observation of ligand and protein dynamics within hemoglobin at work
| Project/Area Number |
16K07326
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | ヘモグロビン / ダイナミクス / X線結晶構造解析 / 光解離 / アロステリー / 光解離法 |
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| Outline of Final Research Achievements |
Hemoglobin is one of the best characterized proteins with respect to structure and function, but the internal ligand diffusion pathways remain obscure and controversial. Here, we capture the CO migration processes in human hemoglobin by crystallography using a high-repetition pulsed laser technique at cryogenic temperatueres. We find that the photodissociated CO molecules migrate along different pathways in the α and β subunit by hopping between the internal cavities with correlated side-chain motions of large nonpolar residues. Our results provide a comprehensive picture of ligand movements in hemoglobin, and highlight the relevance of cavities, nonpolar residues, and distal histidines in facilitating the ligand migration.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト・ヘモグロビンはアロステリック蛋白質の代表格として教科書にも載っており、そのガス配位子結合調節能はよく研究されている。しかし、酸素などのガス分子の通る道筋は結晶構造に見当たらず、ガス分子が蛋白質分子のどこをどのように移動していくのかは謎のままだ。今回の研究成果は、赤血球中のヘモグロビンが酸素を迅速に受け渡しする仕組みの理解につながると期待される。特に、ヘモグロビンが酸素濃度の低い末梢組織にやってきたとき、T状態特有のタンパク質分子内運動を使って酸素を迅速かつ巧妙に外部へ送り出すことを実験的に明らかにした。この発見は、生理学的にも、生物物理学的にも極めて重要な意味がある。
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Report
(5 results)
Research Products
(9 results)
