How do chaperones that they transport other proteins into mitochondria distinguish between their different "cargo proteins"?

The human mitochondrial proteome is estimated to contain more than a thousand proteins, 99% of which are synthesized outside the mitochondria. These proteins are imported inside the mitochondria in very specific places, in one of the membranes, in the inter-membrane space or in the matrix. The molecular mechanisms of this protein import are still poorly understood at the atomic level. A study by the NMR group has shed light on the mechanistic basis of the specificity of the chaperone system of the intermembrane space of the mitochondria. Sucec et al. studied how two chaperones which are structurally homologous but have different functions, interact with different membrane-protein precursors. By combining different techniques including NMR, Small Angle X-ray Scattering (SAXS), Analytical Ultracentrifugation (AUC) and Molecular Dynamics simulations and other biophysical / biochemical approaches, they were able to demonstrate the formation different types of complex chaperones. The delicate balance between promiscuity and specificity that these chaperones must satisfy is the result of a combination of hydrophobic and hydrophilic interactions towards different client proteins. This work contributes to the advancement of knowledge on the biogenesis of mitochondria, and more generally on the functioning of chaperone proteins, important players in the homeostasis of cellular proteins.

Structural basis of client specificity in mitochondrial membrane-protein chaperones. Sucec I, Wang Y, Dakhlaoui O, Weinhaupl K, Jores T, Costa D, Hessel A, Brennich M, Rapaport D, Lindorff-Larsen K, Bersch B and Schanda P. Science Advances 2020;6(51):eabd0263

Contact : Paul Schanda (Biomolecular NMR Spectroscopy group)