Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution

Abstract

Treble clef (TC) zinc fingers constitute a large fold-group of structural zinc-binding protein domains that mediate numerous cellular functions. We have analysed the sequence, structure, and function relationships among all TCs in the Protein Data Bank. This led to the identification of novel TCs, such as lsr2, YggX and TFIIIC τ 60 kDa subunit, and prediction of a nuclease-like function for the DUF1364 family. The structural malleability of TCs is evident from the many examples with variations to the core structural elements of the fold. We observe domains wherein the structural core of the TC fold is circularly permuted, and also some examples where the overall fold resembles both the TC motif and another unrelated fold. All extant TC families do not share a monophyletic origin, as several TC proteins are known to have been present in the last universal common ancestor and the last eukaryotic common ancestor. We identify several TCs where the zinc-chelating site and residues are not merely responsible for structure stabilization but also perform other functions, such as being redox active in C1B domain of protein kinase C, a nucleophilic acceptor in Ada and catalytic in organomercurial lyase, MerB.

Systematic classification of the His-Me finger superfamily

“…DUF1364 clusters with DUF968, together forming group 7, and includes the Escherichia coli prophage protein ybcO of known structure (PDB ID: 3g27). A manual structure superposition to other members of this superfamily unarguably classifies DUF1364 as a His-Me finger domain, which agrees with the hypothesis made previously ( 46 ).…”

“…Additionally, we identified seven Pfam families: DUF1364, RE_Alw26IDE, Tox-HNH-HHH, Tox-HNH-EHHH, Tox-SHH, Tox-GHH and Tox-GHH2, which have not been assigned to the His-Me finger Pfam clan but are predicted to have both the His-Me finger fold and the active site ( 46 – 48 ). DUF1364 clusters with DUF968, together forming group 7, and includes the Escherichia coli prophage protein ybcO of known structure (PDB ID: 3g27).…”

Comparative Genomics of Two New HF1-like Haloviruses

“…predominantly function as interaction modules that can bind to nucleic acids, proteins and other small molecules, including lipids [31,32]. Serpecor1 carries 23 annotated genes specifying CxxC motif proteins, and Hardycor2 carries 21 such genes.…”

“…A significant proportion of genes of the HF1-group viruses code for proteins containing one or more CxxC motifs, which are signature features of zinc-finger (ZF) domains. In general, ZF domains predominantly function as interaction modules that can bind to nucleic acids, proteins and other small molecules, including lipids [31,32]. Serpecor1 carries 23 annotated genes specifying CxxC motif proteins, and Hardycor2 carries 21 such genes.…”

An original structural fold underlies the multitask P1, a silencing suppressor encoded by the Rice yellow mottle virus

“…According to the crystal structure, both Cys64 and Cys67 belong to a  turn between strands D and E, whereas Cys95 is located at the beginning of helix 2 ( Fig 2B-C). Hence, ZnF1 belongs to the treble clef group, albeit not a canonical form as Cys92 does not belong to helix 2 (Krishna et al, 2003;Kaur & Subramanian, 2016). Another remarkable feature of P1_1-100 is the presence of a helix harboring a lysine (Lys17) completely solvent exposed ( Fig 2D).…”