气候变化领域集成服务门户(CCPortal): Direct observation of ligand migration within human hemoglobin at work

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DOI	10.1073/pnas.1913663117
	Direct observation of ligand migration within human hemoglobin at work
	Shibayama N.; Sato-Tomita A.; Ohki M.; Ichiyanagi K.; Park S.-Y.
发表日期	2020
ISSN	0027-8424
起始页码	4741
结束页码	4748
卷号	117 期号:9
英文摘要	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 captured the CO migration processes in the tense (T), relaxed (R), and second relaxed (R2) quaternary structures of human hemoglobin by crystallography using a high-repetition pulsed laser technique at cryogenic temperatures. We found that in each quaternary structure, the photodissociated CO molecules migrate along distinct pathways in the α and β subunits by hopping between the internal cavities with correlated side chain motions of large nonpolar residues, such as α14Trp(A12), α105Leu(G12), β15Trp(A12), and β71Phe(E15). We also observe electron density evidence for the distal histidine [α58/ β63His(E7)] swing-out motion regardless of the quaternary structure, although less evident in α subunits than in β subunits, suggesting that some CO molecules have escaped directly through the E7 gate. Remarkably, in T-state Fe(II)-Ni(II) hybrid hemoglobins in which either the α or β subunits contain Ni(II) heme that cannot bind CO, the photodissociated CO molecules not only dock at the cavities in the original Fe(II) subunit, but also escape from the protein matrix and enter the cavities in the adjacent Ni(II) subunit even at 95 K, demonstrating the high gas permeability and porosity of the hemoglobin molecule. 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. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Allostery; Hemoglobin; Ligand migration; X-ray crystallography
语种	英语
scopus关键词	carbon monoxide; heme; hemoglobin; hemoglobin alpha chain; hemoglobin beta chain; histidine; iron; leucine; ligand; nickel; nickel complex; phenylalanine; tryptophan; carbon monoxide; fusion protein; heme; hemoglobin; histidine; hybrid hemoglobins; ligand; allosterism; Article; controlled study; electron; gas permeability; human; irradiation; molecule; photolysis; porosity; priority journal; protein function; protein quaternary structure; X ray crystallography; chemistry; diffusion; metabolism; molecular model; protein conformation; protein subunit; Carbon Monoxide; Crystallography, X-Ray; Diffusion; Heme; Hemoglobins; Histidine; Humans; Ligands; Models, Molecular; Protein Conformation; Protein Subunits; Recombinant Fusion Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160311
作者单位	Shibayama, N., Division of Biophysics, Department of Physiology, Jichi Medical University, Tochigi, Shimotsuke, 329-0498, Japan; Sato-Tomita, A., Division of Biophysics, Department of Physiology, Jichi Medical University, Tochigi, Shimotsuke, 329-0498, Japan; Ohki, M., Research Complex at Harwell, Rutherford Appleton Laboratory, Harwell, Didcot, Oxon, OX11 0FA, United Kingdom; Ichiyanagi, K., Division of Biophysics, Department of Physiology, Jichi Medical University, Tochigi, Shimotsuke, 329-0498, Japan; Park, S.-Y., Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Tsurumi, Yokohama, 230-0045, Japan
推荐引用方式 GB/T 7714	Shibayama N.,Sato-Tomita A.,Ohki M.,et al. Direct observation of ligand migration within human hemoglobin at work[J],2020,117(9).
APA	Shibayama N.,Sato-Tomita A.,Ohki M.,Ichiyanagi K.,&Park S.-Y..(2020).Direct observation of ligand migration within human hemoglobin at work.Proceedings of the National Academy of Sciences of the United States of America,117(9).
MLA	Shibayama N.,et al."Direct observation of ligand migration within human hemoglobin at work".Proceedings of the National Academy of Sciences of the United States of America 117.9(2020).