Determinants of Neuroglobin Plasticity Highlighted by Joint Coarse-grained Simulations and High Pressure Crystallography

Overview

Journal Sci Rep

Specialty Science

Date 2017 May 14

PMID 28500341

Citations 4

Authors

Nathalie Colloch

Sophie Sacquin-Mora

Giovanna Avella

Anne-Claire Dhaussy

Thierry Prange

Beatrice Vallone

Eric Girard

Affiliations

Soon will be listed here.

Abstract

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.

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