Conformational Dynamics from Ambiguous Zinc Coordination in the RanBP2-Type Zinc Finger of RBM5. Issue 14 (26th June 2020)

• Record Type: Journal Article
• Authors: Soni, Komal; Martínez-Lumbreras, Santiago; Sattler, Michael
• Is Part Of: Journal of molecular biology. Volume 432:Issue 14(2020)
• Page Start: 4127
• Page End: 4138
• Publication Date: 2020-06-26
• Subjects: RBM5 RNA binding motif protein 5 -- NMR Nuclear magnetic resonance spectroscopy -- RRM RNA recognition motif -- EDTA ethylenediaminetetraacetic acid -- AS alternative splicing -- OCRE OCtamer REpeat -- HSQC heteronuclear single quantum coherence; RBM5 -- RanBP2 Zinc finger -- NMR -- metal-exchange kinetics; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2020.05.012
• Languages: English
• ISSNs: 0022-2836

Abstract

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. Graphical abstract: Unlabelled Image Highlights: RBM5 Zf1 shows conformational exchange conferred by a non-canonical cysteine. Competition between two neighboring cysteines yields dynamic zinc ion coordination. Mutation of the non-canonical cysteine residue confers structural and kinetic stability. Ambiguous zinc coordination might be favorable for the evolution of zinc fingers.