Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography

• Published in: Scientific reports Vol. 7; no. 1; pp. 1858 - 10
• Main Authors: Colloc’h, Nathalie, Sacquin-Mora, Sophie, Avella, Giovanna, Dhaussy, Anne-Claire, Prangé, Thierry, Vallone, Beatrice, Girard, Eric
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 631/114/2397; 631/535/1266; 631/57; Animals; Biochemistry, Molecular Biology; Crystallography; Crystallography, X-Ray; Functional plasticity; Heme; Heme - chemistry; Heme - metabolism; High pressure; Histidine; Humanities and Social Sciences; Humans; Hydrophobicity; Life Sciences; Mice; Models, Molecular; multidisciplinary; Mutation; Neuroglobin; Neuroglobin - chemistry; Neuroglobin - genetics; Neuroglobin - metabolism; Neuroprotection; Plasticity; Pressure; Protein Conformation; Science; Science (multidisciplinary); Structural Biology; Structure-Activity Relationship; X-ray crystallography; Computational models; Biophysics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-02097-1

Investigating the effect of pressure sheds light on the dynamics and plasticity of proteins, intrinsically correlated to functional efficiency. Here we detail the structural response to pressure of neuroglobin (Ngb), a hexacoordinate globin likely to be involved in neuroprotection. In murine Ngb, reversible coordination is achieved by repositioning the heme more deeply into a large internal cavity, the “heme sliding mechanism”. Combining high pressure crystallography and coarse-grain simulations on wild type Ngb as well as two mutants, one (V101F) with unaffected and another (F106W) with decreased affinity for CO, we show that Ngb hinges around a rigid mechanical nucleus of five hydrophobic residues (V68, I72, V109, L113, Y137) during its conformational transition induced by gaseous ligand, that the intrinsic flexibility of the F-G loop appears essential to drive the heme sliding mechanism, and that residue Val 101 may act as a sensor of the interaction disruption between the heme and the distal histidine.