regulation of restriction endodeoxyribonuclease activity / regulation of tolerance induction / calcium-dependent protein kinase regulator activity / positive regulation of myeloid progenitor cell differentiation / regulation of T cell mediated immune response to tumor cell / positive regulation of mismatch repair / negative regulation of apoptotic cell clearance / plasmacytoid dendritic cell activation / negative regulation of RNA polymerase II transcription preinitiation complex assembly / myeloid dendritic cell activation ...regulation of restriction endodeoxyribonuclease activity / regulation of tolerance induction / calcium-dependent protein kinase regulator activity / positive regulation of myeloid progenitor cell differentiation / regulation of T cell mediated immune response to tumor cell / positive regulation of mismatch repair / negative regulation of apoptotic cell clearance / plasmacytoid dendritic cell activation / negative regulation of RNA polymerase II transcription preinitiation complex assembly / myeloid dendritic cell activation / T-helper 1 cell activation / mature B cell differentiation involved in immune response / T-helper 1 cell differentiation / positive regulation of myeloid cell differentiation / positive regulation of toll-like receptor 2 signaling pathway / positive regulation of dendritic cell differentiation / C-X-C chemokine binding / positive regulation of toll-like receptor 9 signaling pathway / negative regulation of CD4-positive, alpha-beta T cell differentiation / neutrophil clearance / B cell homeostatic proliferation / negative regulation of T cell differentiation in thymus / positive regulation of glycogen catabolic process / DN2 thymocyte differentiation / DNA geometric change / pre-B cell allelic exclusion / positive regulation of toll-like receptor 4 signaling pathway / endothelial cell chemotaxis / positive regulation of organ growth / RAGE receptor binding / positive regulation of interleukin-1 production / eye development / Regulation of TLR by endogenous ligand / bubble DNA binding / regulation of behavioral fear response / V(D)J recombination / alphav-beta3 integrin-HMGB1 complex / negative regulation of T cell apoptotic process / myeloid cell differentiation / myeloid progenitor cell differentiation / Apoptosis induced DNA fragmentation / phosphatidylinositol-3,4-bisphosphate binding / inflammatory response to antigenic stimulus / regulation of nucleotide-excision repair / macrophage activation involved in immune response / histone H3K4me3 reader activity / negative regulation of thymocyte apoptotic process / positive regulation of monocyte chemotaxis / MyD88 deficiency (TLR2/4) / positive regulation of monocyte chemotactic protein-1 production / cellular response to interleukin-7 / phosphatidylinositol-3,5-bisphosphate binding / endothelial cell proliferation / positive regulation of chemokine (C-X-C motif) ligand 2 production / glycogen catabolic process / apoptotic cell clearance / supercoiled DNA binding / positive regulation of vascular endothelial cell proliferation / dendritic cell chemotaxis / IRAK4 deficiency (TLR2/4) / DNA binding, bending / positive regulation of DNA binding / regulation of T cell differentiation / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / positive regulation of T cell differentiation / organ growth / T cell lineage commitment / positive regulation of wound healing / phosphatidylserine binding / B cell lineage commitment / positive regulation of sprouting angiogenesis / chemoattractant activity / endoplasmic reticulum-Golgi intermediate compartment / positive regulation of activated T cell proliferation / T cell homeostasis / phosphatidylinositol-3,4,5-trisphosphate binding / TRAF6 mediated NF-kB activation / negative regulation of type II interferon production / DNA topological change / negative regulation of blood vessel endothelial cell migration / positive regulation of interferon-alpha production / positive regulation of interleukin-10 production / Advanced glycosylation endproduct receptor signaling / T cell differentiation / protein kinase activator activity / positive regulation of blood vessel endothelial cell migration / Pyroptosis / protein autoubiquitination / four-way junction DNA binding / condensed chromosome / DNA polymerase binding / phosphatidylinositol-4,5-bisphosphate binding / positive regulation of interleukin-12 production / positive regulation of autophagy / transcription repressor complex / phosphatidylinositol binding / activation of innate immune response / response to glucocorticoid / lung development / positive regulation of interferon-beta production 類似検索 - 分子機能
HMG box A DNA-binding domain, conserved site / HMG box A DNA-binding domain signature. / Recombination-activating protein 1 zinc-finger domain / : / V(D)J recombination-activating protein 1, Zinc finger / RAG nonamer-binding domain / NBD domain profile. / Zinc finger RAG1-type profile. / V(D)J recombination-activating protein 1 / RAG1 importin-binding ...HMG box A DNA-binding domain, conserved site / HMG box A DNA-binding domain signature. / Recombination-activating protein 1 zinc-finger domain / : / V(D)J recombination-activating protein 1, Zinc finger / RAG nonamer-binding domain / NBD domain profile. / Zinc finger RAG1-type profile. / V(D)J recombination-activating protein 1 / RAG1 importin-binding / RAG1 importin binding / Recombination-activation protein 1 (RAG1), recombinase / Recombination activating protein 2 / RAG2 PHD domain / V-D-J recombination activating protein 2 / Recombination activating protein 2, PHD domain / Galactose oxidase/kelch, beta-propeller / HMG-box domain / HMG (high mobility group) box / HMG boxes A and B DNA-binding domains profile. / high mobility group / High mobility group box domain / High mobility group box domain superfamily / Kelch-type beta propeller / Zinc finger, C3HC4 RING-type / Zinc finger, C3HC4 type (RING finger) / Zinc finger, RING-type, conserved site / Zinc finger RING-type signature. / Zinc finger C2H2 superfamily / Ring finger / Zinc finger, FYVE/PHD-type / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type 類似検索 - ドメイン・相同性
: / DNA / DNA (> 10) / High mobility group protein B1 / V(D)J recombination-activating protein 1 / V(D)J recombination-activating protein 2 類似検索 - 構成要素
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
DK036147, DK036144, DK036167
米国
National Institutes of Health/Office of the Director
米国
引用
ジャーナル: Mol Cell / 年: 2018 タイトル: Cracking the DNA Code for V(D)J Recombination. 著者: Min-Sung Kim / Watchalee Chuenchor / Xuemin Chen / Yanxiang Cui / Xing Zhang / Z Hong Zhou / Martin Gellert / Wei Yang / 要旨: To initiate V(D)J recombination for generating the adaptive immune response of vertebrates, RAG1/2 recombinase cleaves DNA at a pair of recombination signal sequences, the 12- and 23-RSS. We have ...To initiate V(D)J recombination for generating the adaptive immune response of vertebrates, RAG1/2 recombinase cleaves DNA at a pair of recombination signal sequences, the 12- and 23-RSS. We have determined crystal and cryo-EM structures of RAG1/2 with DNA in the pre-reaction and hairpin-forming complexes up to 2.75 Å resolution. Both protein and DNA exhibit structural plasticity and undergo dramatic conformational changes. Coding-flank DNAs extensively rotate, shift, and deform for nicking and hairpin formation. Two intertwined RAG1 subunits crisscross four times between the asymmetric pair of severely bent 12/23-RSS DNAs. Location-sensitive bending of 60° and 150° in 12- and 23-RSS spacers, respectively, must occur for RAG1/2 to capture the nonamers and pair the heptamers for symmetric double-strand breakage. DNA pairing is thus sequence-context dependent and structure specific, which partly explains the "beyond 12/23" restriction. Finally, catalysis in crystallo reveals the process of DNA hairpin formation and its stabilization by interleaved base stacking.
根拠: gel filtration, The assembly was made by mixing of RAG1/2, 12RSS, 23RSS, and HMGB1 in 1:1.2:1.2:2 molar ratio. The tetrameric unit was then purified by gel filtration. The molecular weight ...根拠: gel filtration, The assembly was made by mixing of RAG1/2, 12RSS, 23RSS, and HMGB1 in 1:1.2:1.2:2 molar ratio. The tetrameric unit was then purified by gel filtration. The molecular weight marker for gel filtration was used to determine the size of the complex.
タイプ
名称
対称操作
数
identity operation
1_555
x,y,z
1
手法
PISA
単位格子
Length a, b, c (Å)
157.332, 118.830, 198.960
Angle α, β, γ (deg.)
90.000, 100.590, 90.000
Int Tables number
5
Space group name H-M
C121
非結晶学的対称性 (NCS)
NCSドメイン:
ID
Ens-ID
詳細
1
1
(chainDand (resid1through4or (resid5...
2
1
(chainBand (resid1through38or (resid39...
1
2
(chainCand (resid408through503or (resid504...
2
2
(chainAand ((resid408through423and (nameN...
1
3
(chainGandresid33through50) or (chainJandresid8through25)
2
3
(chainFandresid22through39) or (chainIandresid8through25)