Riccio Antonio, Vitagliano Luigi, di Prisco Guido, Zagari Adriana, Mazzarella Lelio
Istituto di Biochimica delle Proteine ed Enzimologia, Consiglio Nazionale delle Ricerche, I-80125 Naples, Italy.
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9801-6. doi: 10.1073/pnas.132182099. Epub 2002 Jul 1.
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-A crystal structure of the main hemoglobin component of the Antarctic fish Trematomus newnesi, in a partial hemichrome form. The two alpha-subunit iron atoms are bound to a CO molecule, whereas in the beta 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 beta heme pocket plays a role in the R --> T transition of tetrameric hemoglobins.
四聚体血红蛋白是研究蛋白质协同性时应用最为广泛的体系。血红蛋白中的别构效应源于氧释放时发生的从松弛（R）态到紧张（T）态的转变。在此，我们报道了南极鱼类新氏南极鱼主要血红蛋白成分处于部分半色素形式下的2.0埃晶体结构。两个α亚基的铁原子与一个CO分子结合，而在β亚基中，远端组氨酸残基是血红素铁的第六个配体。这种处于半色素状态的四聚体血红蛋白结构表明，通常与变性状态相关的远端组氨酸对铁的配位作用，在类似天然的血红蛋白结构中可能是可以耐受的。此外，该结构的三级和四级结构组织的几个特征介于R态和T态之间，与通过光谱和动力学技术获得的R→T过渡态性质高度吻合。对该结构的分析提供了血红素-血红素通讯的详细途径，并且表明β血红素口袋的可塑性在四聚体血红蛋白的R→T转变中发挥作用。
