Publication of IMPRS-LS student Komal Soni
Soni, K., Martínez-Lumbreras, S., and Sattler, M.
J Mol Biol, 2020, [Epub ahead of print].
Conformational dynamics from ambiguous zinc coordination in the RanBP2-type zinc finger of RBM5
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.