The Crystal Structure of a Tetrameric Hemoglobin in a Partial Hemichrome State

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-07, Vol.99 (15), p.9801-9806
• Main Authors: Riccio, Antonio, Vitagliano, Luigi, di Prisco, Guido, Zagari, Adriana, Mazzarella, Lelio
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antarctic Regions; Atoms; Biological Sciences; Biophysics; Crystal structure; Crystallization; Crystallography, X-Ray; Crystals; Dimers; Electron density; Fish; Fishes; Hemoglobins; Hemoglobins - chemistry; Hemoglobins - isolation & purification; Iron; Kinetics; Ligands; Models, Molecular; Molecules; Protein Structure, Quaternary; Protein Structure, Secondary; Protein Subunits; Proteins
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.132182099

Tetrameric hemoglobins are the most widely used systems in studying protein cooperativity. Allosteric effects in hemoglobins arise from the switch between a relaxed (R) state and a tense (T) state occurring upon oxygen release. Here we report the 2.0-Å crystal structure of the main hemoglobin component of the Antarctic fish Trematomus newnesi, in a partial hemichrome form. The two α-subunit iron atoms are bound to a CO molecule, whereas in the β subunits the distal histidine residue is the sixth ligand of the heme iron. This structure, a tetrameric hemoglobin in the hemichrome state, demonstrates that the iron coordination by the distal histidine, usually associated with denaturing states, may be tolerated in a native-like hemoglobin structure. In addition, several features of the tertiary and quaternary organization of this structure are intermediate between the R and T states and agree well with the R → T transition state properties obtained by spectroscopic and kinetic techniques. The analysis of this structure provides a detailed pathway of heme-heme communication and it indicates that the plasticity of the β heme pocket plays a role in the R → T transition of tetrameric hemoglobins.