Solution Structure of an Archaeal DNA Binding Protein with an Eukaryotic Zinc Finger Fold

Abstract

While the basal transcription machinery in archaea is eukaryal-like, transcription factors in archaea and their viruses are usually related to bacterial transcription factors. Nevertheless, some of these organisms show predicted classical zinc fingers motifs of the C2H2 type, which are almost exclusively found in proteins of eukaryotes and most often associated with transcription regulators. In this work, we focused on the protein AFV1p06 from the hyperthermophilic archaeal virus AFV1. The sequence of the protein consists of the classical eukaryotic C2H2 motif with the fourth histidine coordinating zinc missing, as well as of N- and C-terminal extensions. We showed that the protein AFV1p06 binds zinc and solved its solution structure by NMR. AFV1p06 displays a zinc finger fold with a novel structure extension and disordered N- and C-termini. Structure calculations show that a glutamic acid residue that coordinates zinc replaces the fourth histidine of the C2H2 motif. Electromobility gel shift assays indicate that the protein binds to DNA with different affinities depending on the DNA sequence. AFV1p06 is the first experimentally characterised archaeal zinc finger protein with a DNA binding activity. The AFV1p06 protein family has homologues in diverse viruses of hyperthermophilic archaea. A phylogenetic analysis points out a common origin of archaeal and eukaryotic C2H2 zinc fingers.

Comparative Genomics of Two New HF1-like Haloviruses

“…In earlier work, Brz, a small zinc-finger protein, was shown to regulate multiple genes, including bop, crtB1, OE3107F and OE3095R [46]. A more distant example is AFV1p06, a small (59 aa) protein encoded by the thermophilic archaeal virus AFV1 [47]. AFV1p06 carries a eukaryal ZF fold, can bind DNA, and is a potential transcriptional regulator that belongs to a protein family with members in many thermophilic viruses and archaea.…”

Differential effects of zinc binding on structured and disordered regions in the multidomain STIL protein

“…Zn 2+ binding to disordered regions was shown to induce a disorder to order transition and gain of structure in many cases 36 – 38 or lead to oligomerization, mainly aggregation, of IDPs. 11 , 12 , 39 Here we show that binding of Zn 2+ ions induces different effects on structured and disordered domains in the same protein: while binding of Zn 2+ induced structural changes in the structured STIL NTD, it did not induce structural rearrangement or gain of structure of the disordered domain of STIL.…”

The Wonderful World of Archaeal Viruses

“…AvtR also acts as a transcription activator (33). High-resolution structural information is available for several DNA-binding proteins with ribbon-helix-helix, helix-turn-helix, and zinc finger structural motifs from different viruses (32,42) (Figure 5), but the role of these proteins in transcription regulation remains to be verified.…”