2JWO

A PHD finger motif in the C-terminus of RAG2 modulates recombination activity

「2A23」から置き換えられました

2JWO の概要

• エントリーDOI: 10.2210/pdb2jwo/pdb
• 分子名称: V(D)J recombination-activating protein 2, ZINC ION (2 entities in total)
• 機能のキーワード: v(d)j recombination, phosphoinositide signaling, rag2, phd domain, dna recombination, dna-binding, endonuclease, hydrolase, nuclease, nucleus, recombination
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Nucleus: P21784
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9491.32

構造登録者

Ivanov, D.,Hyberts, S.G.,Sun, Z.,Wagner, G. (登録日: 2007-10-17, 公開日: 2007-11-06, 最終更新日: 2024-05-29)

主引用文献

Elkin, S.K.,Ivanov, D.,Ewalt, M.,Ferguson, C.G.,Hyberts, S.G.,Sun, Z.Y.,Prestwich, G.D.,Yuan, J.,Wagner, G.,Oettinger, M.A.,Gozani, O.P.
A PHD finger motif in the C terminus of RAG2 modulates recombination activity.
J.Biol.Chem., 280:28701-28710, 2005

PubMed Abstract: The RAG1 and RAG2 proteins catalyze V(D)J recombination and are essential for generation of the diverse repertoire of antigen receptor genes and effective immune responses. RAG2 is composed of a "core" domain that is required for the recombination reaction and a C-terminal nonessential or "non-core" region. Recent evidence has emerged arguing that the non-core region plays a critical regulatory role in the recombination reaction, and mutations in this region have been identified in patients with immunodeficiencies. Here we present the first structural data for the RAG2 protein, using NMR spectroscopy to demonstrate that the C terminus of RAG2 contains a noncanonical PHD finger. All of the non-core mutations of RAG2 that are implicated in the development of immunodeficiencies are located within the PHD finger, at either zinc-coordinating residues or residues adjacent to an alpha-helix on the surface of the domain that participates in binding to the signaling molecules, phosphoinositides. Functional analysis of disease and phosphoinositide-binding mutations reveals novel intramolecular interactions within the non-core region and suggests that the PHD finger adopts two distinct states. We propose a model in which the equilibrium between these states modulates recombination activity. Together, these data identify the PHD finger as a novel and functionally important domain of RAG2.

PubMed: 15964836
DOI: 10.1074/jbc.M504731200

実験手法

SOLUTION NMR