title: Structural characterization of recombinant human myoglobin isoforms by (1)H and (129)Xe NMR and molecular dynamics simulations.
abstract: Myoglobin (Mb), the main cytosolic oxygen storage/deliver protein, is also known to interact with different small ligands exerting other fundamental physiological roles. In Humans up to five different Mb isoforms are present. The two most expressed ones (>90%) differ only at the 54th position, K54 (Mb-I) and E54 (Mb-II) respectively. High-altitude populations are characterized by a higher Mb concentration in skeletal muscle, totally attributable to Mb-II, as well as a higher efficiency of locomotion, leading to the hypothesis of a cause-effect relationship with the evolutionary response to the high-altitude hypoxic environment. In this work, a first structural characterization of the two more expressed human Mb isoforms has been carried out. In particular, a detailed (1)H and (129)Xe NMR study was aimed to characterize the structure of the hydrophobic cavities around the heme group. Experimental results have been compared to those from MD simulations, i.e. volume fluctuations and occurrence. Electronic structure of the heme ring ground state resulted to be comparable for the two investigated isoforms, despite the single point mutation at position 54. However, the use of (129)Xe as a probe revealed small but significant modifications in the structure of internal cavities. MD simulations supported NMR results indicating interesting structural/dynamical differences in the average volume and occurrence of the main cavities lining Mb prosthetic group.
authors.affiliation: Università di Milano, Dipartimento di Scienze e Tecnologie Biomediche, Italy. maristella.gussoni@unimi.it
authors.forename: Maristella
authors.initials: M
authors.lastname: Gussoni
authors.forename: Mariano Andrea
authors.initials: MA
authors.lastname: Scorciapino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vezzoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Anedda
authors.forename: Fulvia
authors.initials: F
authors.lastname: Greco
authors.forename: Matteo
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Mariano
authors.initials: M
authors.lastname: Casu
mesh_terms: D018360:Crystallography, X-Ray; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009211:Myoglobin / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D014978:Xenon / Q000737:chemistry
chemical_list: D009211:Myoglobin; D020033:Protein Isoforms; D011994:Recombinant Proteins; D014978:Xenon; D006418:Heme; D006859:Hydrogen; D010100:Oxygen