Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1.
V(D)J recombination generates functional immunoglobulin and T-cell receptor genes in developing lymphocytes. The recombination-activating gene 1 (RAG1) and RAG2 proteins catalyze site-specific DNA cleavage in this recombination process. Biochemical studies have identified catalytically active regions of each protein, referred to as the core regions. Here, we review our progress in the identification and characterization, in biophysical and biochemical terms, of topologically independent domains within both the non-core and core regions of RAG1. Previous characterizations of a structural domain identified in the non-core region of RAG1 from residues 265-380, referred to as the zinc-binding dimerization domain, are discussed. This domain contains two zinc-binding motifs, a RING finger and a C2H2 zinc finger. Core RAG1 also consists of multiple domains, each of which functions individually in one or more of the essential macromolecular interactions formed by the intact core protein. Two structural domains referred to as the central and the C-terminal domains that include residues 528-760 and 761-979 of RAG1, respectively, have been identified. The interactions of the central and C-terminal domains in core RAG1 with the recombination signal sequence (RSS) have contributed additional insight to a developing model for the RAG1-RSS complex.
De
Pallabi
P
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Rodgers
Karla K
KK
D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins; D021382:Protein Sorting Signals / Q000502:physiology; D017434:Protein Structure, Tertiary; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein