Structural classification of zinc fingers: SURVEY AND SUMMARY

Abstract

Zinc fingers are small protein domains in which zinc plays a structural role contributing to the stability of the domain. Zinc fingers are structurally diverse and are present among proteins that perform a broad range of functions in various cellular processes, such as replication and repair, transcription and translation, metabolism and signaling, cell proliferation and apoptosis. Zinc fingers typically function as interaction modules and bind to a wide variety of compounds, such as nucleic acids, proteins and small molecules. Here we present a comprehensive classification of zinc finger spatial structures. We find that each available zinc finger structure can be placed into one of eight fold groups that we define based on the structural properties in the vicinity of the zinc-binding site. Three of these fold groups comprise the majority of zinc fingers, namely, C2H2-like finger, treble clef finger and the zinc ribbon. Evolutionary relatedness of proteins within fold groups is not implied, but each group is divided into families of potential homologs. We compare our classification to existing groupings of zinc fingers and find that we define more encompassing fold groups, which bring together proteins whose similarities have previously remained unappreciated. We analyze functional properties of different zinc fingers and overlay them onto our classification. The classification helps in understanding the relationship between the structure, function and evolutionary history of these domains. The results are available as an online database of zinc finger structures.

Relationships between serum selenium and zinc concentrations versus profibrotic and proangiogenic cytokines (FGF-19 and endoglin) in patients with alcoholic liver cirrhosis

“…It stabilises the structure of zinc fingers, plays an important role in DNA transcription and repair, division and apoptosis of cells. Zinc fingers stabilise the structure of transcription factors, steroid hormones, the thyroid and vitamin D [26]. The deficiency of zinc induces oxidative stress, causing hepatitis and decreasing the response to infections and toxic substances [27].…”

Redox‐dependent disulfide bond formation in SAP30L corepressor protein: Implications for structure and function

“…A total of 22 specific tryptic peptides were identified in these conditions, accounting for 100% sequence coverage (Table II). No disulfidecontaining peptides were detected, including the tryptic peptide [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] with adjacent cysteine residues. Yet, formation of intramolecular disulfide bonds were observed after a short-term storage, even in reducing conditions, indicating that an oxidized form is favored in small tryptic peptides having free thiol groups.…”

“…This peptide was further subjected to ECD-MS/MS measurement, proving that the disulfide bond is, indeed, formed between the two adjacent cysteinyl residues (i.e., a vicinal disulfide). The ECD spectrum of [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] 21 ion showed multiple z-ions up to the formed disulfide bond (Supporting Information Fig. S5).…”

“…All peptides containing free cysteines were absent, indicating that the disulfide bonds are formed before digestion and oxidation does not occur at low pH. Five of the peptides were identified to contain disulfide bonds; the peptides [1][2][3][4][5][6][7][8][9][10][11][12][13] and confirmed again the vicinal disulfide bond between the adjacent Cys29 and Cys30, while the three larger disulfide-linked peptides confirmed the other disulfide bond between Cys38 and Cys74. Therefore, it seems that pepsin could be preferred over trypsin for identifying redox-active disulfide bonds in proteins since even in the absence of a reducing agent, no auto-oxidation or mixed disulfide bonds were observed following digestion.…”

“…ZnF proteins are typically involved in proteinnucleic acid and protein-protein interactions, although the concept of a zinc finger is vague and several different zinc binding motifs have been characterized. 5 In a zinc finger, the Zn(II) ion is most frequently coordinated by four cysteine residues, having tetrahedral binding geometry. 6 ZnF-based redox switches are involved in many physiological events such as cell growth and differentiation, transcription, translation, signal transduction, and apoptosis.…”