Domain

Zinc finger, V(D)J recombination-activating protein 1 (IPR019485)

Short name: Znf_VDJ_recomb-activ_1

Domain relationships

Description

During lymphocyte development, the genes encoding immunoglobulins and T-cell receptors are assembled from variable (V), diversity (D), and joining (J) gene segments. This combinatorial process, known as V(D)J recombination, allows the generation of an enormous range of binding specificities from a limited amount of genetic information. The V(D)J recombination-activating proteins 1 and 2 (RAG1 and RAG2) form a complex that initiates this process by binding to the conserved recombination signal sequences (RSS) and introducing a double-strand break between the RSS and the adjacent coding segment. These breaks are generated in two steps, nicking of one strand (hydrolysis), followed by hairpin formation (transesterification). RAG1/2 has also been shown to function as a transposase in vitro, and to possess RSS-independent endonuclease activity (end processing) and hairpin opening. RAG1 alone can bind to RSS but stable, efficient binding requires RAG2. All known catalytic activities require the presence of both proteins. For more information see [PMID: 18066091].

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 [PMID: 10529348, PMID: 15963892, PMID: 15718139, PMID: 17210253, PMID: 12665246]. 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 [PMID: 11179890]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

C2H2-type (classical) zinc fingers (Znf) were the first class to be characterised. They contain a short beta hairpin and an alpha helix (beta/beta/alpha structure), where a single zinc atom is held in place by Cys(2)His(2) (C2H2) residues in a tetrahedral array. C2H2 Znf's can be divided into three groups based on the number and pattern of fingers: triple-C2H2 (binds single ligand), multiple-adjacent-C2H2 (binds multiple ligands), and separated paired-C2H2 [PMID: 11361095]. C2H2 Znf's are the most common DNA-binding motifs found in eukaryotic transcription factors, and have also been identified in prokaryotes [PMID: 10664601]. Transcription factors usually contain several Znf's (each with a conserved beta/beta/alpha structure) capable of making multiple contacts along the DNA, where the C2H2 Znf motifs recognise DNA sequences by binding to the major groove of DNA via a short alpha-helix in the Znf, the Znf spanning 3-4 bases of the DNA [PMID: 10940247]. C2H2 Znf's can also bind to RNA and protein targets [PMID: 18253864].

This entry represents a C2H2-type zinc-finger domain found in the RAG1 protein. The structure contains the characteristic two-stranded beta-sheet and alpha-helix of a classical zinc-finger. The domain binds one zinc and, in complex with an adjacent RING-type zinc finger domain, helps to stabilise the whole of the dimerisation region of recombination activating protein 1 (RAG1) [PMID: 9228952]. The function of the whole is to bind double-stranded DNA.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0016881 acid-amino acid ligase activity
GO:0016788 hydrolase activity, acting on ester bonds

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
Pfam