InterPro domain: IPR007853

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [ 1 , 2 , 3 , 4 , 5 ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [ 6 ]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

The DNL-type zinc finger is found in Tim15, a zinc finger protein essential for protein import into mitochondria. Mitochondrial functions rely on the correct transport of resident proteinssynthesized in the cytosol to mitochondria. Protein import into mitochondriais mediated by membrane protein complexes, protein translocators, in the outerand inner mitochondrial membranes, in cooperation with their assistantproteins in the cytosol, intermembrane space and matrix. Proteins destined tothe mitochondrial matrix cross the outer membrane with the aid of the outermembrane translocator, the tOM40 complex, and then the inner membrane with theaid of the inner membrane translocator, the TIM23 complex, and mitochondrial motor and chaperone (MMC) proteins including mitochondrial heat-shock protein 70 (mtHsp70), and translocase in the inner mitochondrialmembrane (Tim)15. Tim15 is also known as zinc finger motif (Zim)17 or mtHsp70escort protein (Hep)1. Tim15 contains a zinc-finger motif (CXXCand CXXC) of ~100 residues, which has been named DNL after a short C-terminalmotif of D(N/H)L [ 7 , 8 , 9 ].

The DNL-type zinc finger is an L-shaped molecule. The twoCXXC motifs are located at the end of the L, and are sandwiched by two-stranded antiparallel beta-sheets. Two short alpha-helices constitute anotherleg of the L. The outer (convex) face of the L has a large acidic groove,which is lined with five acidic residues, whereas the inner (concave) face ofthe L has two positively charged residues, next to the CXXC motifs [ 10 ].

This entry represents the DNL-type zinc finger.

1. Zinc finger peptides for the regulation of gene expression. J. Mol. Biol. 293, 215-8
2. Multiple modes of RNA recognition by zinc finger proteins. Curr. Opin. Struct. Biol. 15, 367-73
3. Zinc finger proteins: getting a grip on RNA. Curr. Opin. Struct. Biol. 15, 94-8
4. Sticky fingers: zinc-fingers as protein-recognition motifs. Trends Biochem. Sci. 32, 63-70
5. Zinc fingers--folds for many occasions. IUBMB Life 54, 351-5
6. Zinc finger proteins: new insights into structural and functional diversity. Curr. Opin. Struct. Biol. 11, 39-46
7. Zim17, a novel zinc finger protein essential for protein import into mitochondria. J. Biol. Chem. 279, 50243-9
8. Identification of a novel member of yeast mitochondrial Hsp70-associated motor and chaperone proteins that facilitates protein translocation across the inner membrane. FEBS Lett. 579, 507-11
9. Structural basis of functional cooperation of Tim15/Zim17 with yeast mitochondrial Hsp70. EMBO Rep. 8, 664-70