論文

2020年3月

Direct observation of ligand migration within human hemoglobin at work

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Naoya Shibayama
  • ,
  • Ayana Sato-Tomita
  • ,
  • Mio Ohki
  • ,
  • Kouhei Ichiyanagi
  • ,
  • Sam-Yong Park

117
9
開始ページ
4741
終了ページ
4748
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1913663117
出版者・発行元
NATL ACAD SCIENCES

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 photo-dissociated CO molecules migrate along distinct pathways in the a and beta subunits by hopping between the internal cavities with correlated side chain motions of large nonpolar residues, such as alpha 14Trp(A12), alpha 105Leu(G12), beta 15Trp(A12), and beta 71Phe(E15). We also observe electron density evidence for the distal histidine [alpha 58/beta 63His(E7)] swing-out motion regardless of the quaternary structure, although less evident in alpha subunits than in beta 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 alpha or beta 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.


リンク情報
DOI
https://doi.org/10.1073/pnas.1913663117
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000518473500047&DestApp=WOS_CPL
URL
http://www.pnas.org/syndication/doi/10.1073/pnas.1913663117
URL
https://syndication.highwire.org/content/doi/10.1073/pnas.1913663117

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