Studies of the conformational changes on the ribosomal GTPase EFL1 using SAXS

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Abstract

Ribosome biogenesis is closely linked to the cell growth and proliferation. Dysregulation of this process causes several diseases collectively known as ribosomopathies. One of them is the Shwachman-Diamond Syndrome, and the SBDS protein mutated in this disease participates with EFL1 in the cytoplasmic maturation of the 60S subunit. Recently, we have shown that the interaction of EFL1 with SBDS resulted in a decrease of the Michaelis-Menten constant (KM) for GTP and thus SBDS acts as a GEF for EFL1 (1). Subsequent studies demonstrated that SBDS greatly debilitates the interaction of EFL1 with GDP without altering that for GTP. The interaction of EFL1 alone or in complex with SBDS to guanine nucleotides is followed by a conformational rearrangement. Understanding the molecular strategy used by SBDS to disrupt the binding of EFL1 for GDP and the associated conformational changes will be key to understand their mode of action and alterations occurring in the disease. The structure of the GTPase EFL1 is not known and its crystallization has been unsuccessful at least in our hands. In this study, we aim to show the conformational changes resulting from the interactions between EFL1 and its binding partners, the SBDS protein and the guanine nucleotides using SAXS technique (2, 3). SAXS will provide structural information of the proteins and their conformational changes (4). For the SAXS data analysis we have built models of EFL1 using by EF-2 as homology template and of SBDS using the crystal structures of the archaea orthologues.

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  • D. Siliqi; N. Sanchez-Puig; E. de la Mora; A. Méndez-Godoy; D. Altamura; C. Giannini; T. Sibillano; M. Saviano

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Anno di pubblicazione

2015

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