- EMDB-60598: Structure of CTF18-PCNA with ATP and Mg2+ -
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基本情報
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データベース: EMDB / ID: EMD-60598
タイトル
Structure of CTF18-PCNA with ATP and Mg2+
マップデータ
Sharpened map.
試料
複合体: CTF18-PCNA
複合体: CTF18
タンパク質・ペプチド: Chromosome transmission fidelity protein 18 homolog
タンパク質・ペプチド: Replication factor C subunit 2
タンパク質・ペプチド: Replication factor C subunit 5
タンパク質・ペプチド: Replication factor C subunit 4
タンパク質・ペプチド: Replication factor C subunit 3
複合体: PCNA
タンパク質・ペプチド: Proliferating cell nuclear antigen
リガンド: ADENOSINE-5'-TRIPHOSPHATE
リガンド: MAGNESIUM ION
リガンド: ADENOSINE-5'-DIPHOSPHATE
キーワード
CTF18-RFC / human clamp loader / PCNA / sliding clamp / complex / ATP / DNA BINDING PROTEIN
機能・相同性
機能・相同性情報
Elg1 RFC-like complex / DNA replication factor C complex / Ctf18 RFC-like complex / positive regulation of deoxyribonuclease activity / dinucleotide insertion or deletion binding / PCNA-p21 complex / mitotic telomere maintenance via semi-conservative replication / DNA clamp loader activity / purine-specific mismatch base pair DNA N-glycosylase activity / nuclear lamina ...Elg1 RFC-like complex / DNA replication factor C complex / Ctf18 RFC-like complex / positive regulation of deoxyribonuclease activity / dinucleotide insertion or deletion binding / PCNA-p21 complex / mitotic telomere maintenance via semi-conservative replication / DNA clamp loader activity / purine-specific mismatch base pair DNA N-glycosylase activity / nuclear lamina / positive regulation of DNA-directed DNA polymerase activity / Polymerase switching / MutLalpha complex binding / Telomere C-strand (Lagging Strand) Synthesis / Processive synthesis on the lagging strand / PCNA complex / Removal of the Flap Intermediate / Processive synthesis on the C-strand of the telomere / Polymerase switching on the C-strand of the telomere / Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) / Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) / Removal of the Flap Intermediate from the C-strand / Transcription of E2F targets under negative control by DREAM complex / replisome / response to L-glutamate / HDR through Single Strand Annealing (SSA) / DNA strand elongation involved in DNA replication / response to dexamethasone / DNA synthesis involved in DNA repair / histone acetyltransferase binding / Impaired BRCA2 binding to RAD51 / DNA polymerase processivity factor activity / leading strand elongation / G1/S-Specific Transcription / nuclear replication fork / replication fork processing / Presynaptic phase of homologous DNA pairing and strand exchange / SUMOylation of DNA replication proteins / PCNA-Dependent Long Patch Base Excision Repair / ATP-dependent activity, acting on DNA / response to cadmium ion / translesion synthesis / estrous cycle / mismatch repair / Activation of ATR in response to replication stress / cyclin-dependent protein kinase holoenzyme complex / base-excision repair, gap-filling / DNA polymerase binding / liver regeneration / epithelial cell differentiation / positive regulation of DNA repair / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / Translesion synthesis by REV1 / Translesion synthesis by POLK / Translesion synthesis by POLI / replication fork / Gap-filling DNA repair synthesis and ligation in GG-NER / positive regulation of DNA replication / nuclear estrogen receptor binding / male germ cell nucleus / Termination of translesion DNA synthesis / Recognition of DNA damage by PCNA-containing replication complex / Translesion Synthesis by POLH / G2/M DNA damage checkpoint / receptor tyrosine kinase binding / HDR through Homologous Recombination (HRR) / Dual Incision in GG-NER / DNA-templated DNA replication / cellular response to xenobiotic stimulus / cellular response to hydrogen peroxide / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / cellular response to UV / response to estradiol / E3 ubiquitin ligases ubiquitinate target proteins / heart development / chromatin organization / Processing of DNA double-strand break ends / Regulation of TP53 Activity through Phosphorylation / damaged DNA binding / chromosome, telomeric region / DNA replication / nuclear body / DNA repair / centrosome / chromatin binding / chromatin / protein-containing complex binding / enzyme binding / negative regulation of transcription by RNA polymerase II / ATP hydrolysis activity / DNA binding / extracellular exosome / nucleoplasm / ATP binding / identical protein binding / nucleus / membrane / cytosol 類似検索 - 分子機能
: / Replication factor C subunit 3, C-terminal domain / RCF1/5-like, AAA+ ATPase lid domain / Replication factor C, C-terminal / Replication factor C C-terminal domain / : / DNA polymerase III, delta subunit / : / DNA polymerase III, clamp loader complex, gamma/delta/delta subunit, C-terminal / Proliferating cell nuclear antigen signature 2. ...: / Replication factor C subunit 3, C-terminal domain / RCF1/5-like, AAA+ ATPase lid domain / Replication factor C, C-terminal / Replication factor C C-terminal domain / : / DNA polymerase III, delta subunit / : / DNA polymerase III, clamp loader complex, gamma/delta/delta subunit, C-terminal / Proliferating cell nuclear antigen signature 2. / Proliferating cell nuclear antigen, PCNA, conserved site / Proliferating cell nuclear antigen signature 1. / Proliferating cell nuclear antigen, PCNA / Proliferating cell nuclear antigen, PCNA, N-terminal / Proliferating cell nuclear antigen, PCNA, C-terminal / Proliferating cell nuclear antigen, N-terminal domain / Proliferating cell nuclear antigen, C-terminal domain / : / ATPase family associated with various cellular activities (AAA) / ATPase, AAA-type, core / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Proliferating cell nuclear antigen / Replication factor C subunit 4 / Replication factor C subunit 2 / Replication factor C subunit 5 / Replication factor C subunit 3 / Chromosome transmission fidelity protein 18 homolog 類似検索 - 構成要素
ジャーナル: bioRxiv / 年: 2025 タイトル: Structure of the human CTF18-RFC clamp loader bound to PCNA. 著者: Giuseppina R Briola / Muhammad Tehseen / Amani Al-Amodi / Grace Young / Ammar U Danazumi / Phong Quoc Nguyen / Christos G Savva / Mark Hedglin / Samir M Hamdan / Alfredo De Biasio / 要旨: Sliding clamps like PCNA are crucial processivity factors for replicative polymerases, requiring specific clamp loaders for loading onto DNA. The human alternative clamp loader CTF18-RFC interacts ...Sliding clamps like PCNA are crucial processivity factors for replicative polymerases, requiring specific clamp loaders for loading onto DNA. The human alternative clamp loader CTF18-RFC interacts with the leading strand polymerase Pol ε and loads PCNA onto primer/template DNA using its RFC pentameric module. Here, we provide a structural characterization of the human CTF18-RFC complex and its interaction with PCNA. Our cryo-EM data support that the Ctf8 and Dcc1 subunits of CTF18-RFC, which form the regulatory module interacting with Pol ε, are flexibly tethered to the RFC module. A 2.9 Å cryo-EM structure shows the RFC module bound to PCNA in an auto-inhibited conformation similar to the canonical RFC loader, marking the initial step of the clamp-loading reaction. The unique RFC1 (Ctf18) large subunit of CTF18-RFC, which based on the cryo-EM map shows high relative flexibility, is anchored to PCNA through an atypical low-affinity PIP box in the AAA+ domain and engages the RFC5 subunit using a novel β-hairpin at the disordered N-terminus. We show that deletion of this β-hairpin impairs the CTF18-RFC-PCNA complex stability, slows down clamp loading, and decreases the rate of primer synthesis by Pol ε. Our research identifies distinctive structural characteristics of the human CTF18-RFC complex, providing insights into its role in PCNA loading and the stimulation of leading strand synthesis by Pol ε.