6L5X

Carbonmonoxy human hemoglobin A in the R2 quaternary structure at 95 K: Light (2 min)

Summary for 6L5X

• Entry DOI: 10.2210/pdb6l5x/pdb
• Related: 6KA9 6KAE 6KAH 6KAI 6KAO 6KAP 6KAQ 6KAR 6KAS 6KAT 6KAU 6KAV 6L5V 6L5W
• Descriptor: Hemoglobin subunit alpha, Hemoglobin subunit beta, PROTOPORPHYRIN IX CONTAINING FE, ... (5 entities in total)
• Functional Keywords: hemoglobin, photolysis, oxygen transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 64659.09

Authors

Shibayama, N.,Park, S.Y.,Ohki, M.,Sato-Tomita, A. (deposition date: 2019-10-24, release date: 2020-02-19, Last modification date: 2023-11-22)

Primary citation

Shibayama, N.,Sato-Tomita, A.,Ohki, M.,Ichiyanagi, K.,Park, S.Y.
Direct observation of ligand migration within human hemoglobin at work.
Proc.Natl.Acad.Sci.USA, 117:4741-4748, 2020

PubMed Abstract: 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.

PubMed: 32071219
DOI: 10.1073/pnas.1913663117

Experimental method

X-RAY DIFFRACTION (1.65 Å)