Conformational Dynamics From Ambiguous Zinc Coordination in the RanBP2-Type Zinc Finger of RBM5

J Mol Biol. 2020 Jun 26;432(14):4127-4138. doi: 10.1016/j.jmb.2020.05.012. Epub 2020 May 22.

Abstract

The multi-domain RNA binding protein RBM5 is a molecular signature of metastasis. RBM5 regulates alternative splicing of apoptotic genes including the cell death receptor Fas and the initiator Caspase-2. The RBM5 RanBP2-type zinc finger (Zf1) is known to specifically recognize single-stranded RNAs with high affinity. Here, we study the structure and conformational dynamics of the Zf1 zinc finger of human RBM5 using NMR. We show that the presence of a non-canonical cysteine in Zf1 kinetically destabilizes the protein. Metal-exchange kinetics show that mutation of the cysteine establishes high-affinity coordination of the zinc. Our data indicate that selection of such a structurally destabilizing mutation during the course of evolution could present an opportunity for functional adaptation of the protein.

Keywords: NMR; RBM5; RanBP2 Zinc finger; metal-exchange kinetics.