Article
Multidisciplinary Sciences
Thang Quyet Nguyen, Seri Koh, Jiin Kwon, Soyeon Jang, Wonchull Kang, Jin Kuk Yang
Summary: p97 is a human AAA+ ATPase involved in various cellular processes. METTL21D is a Lys-specific methyltransferase that methylates Lys315 of p97, known as VCPKMT. The structures of S-adenosyl-L-methionine-bound VCPKMT and S-adenosyl-L-homocysteine-bound VCPKMT complexed with p97 N/D1 were reported, revealing the molecular details of p97 recognition and methylation by VCPKMT. The study also investigated the enhancement of p97 methylation through cooperation between VCPKMT and ASPL C-terminus.
Review
Medicine, Research & Experimental
Jiahui Fu, Jin Zhang, Xiya Chen, Zhiying Liu, Xuetao Yang, Zhendan He, Yue Hao, Bo Liu, Dahong Yao
Summary: ATPase family AAA domain-containing protein 2 (ATAD2) is a new oncogene closely associated with epigenetic modifications in human cancers. It functions as a coactivator of transcription factors and regulates the expression of downstream oncogenes or tumor suppressors. The dominant structure of ATAD2 makes it a potential therapeutic target in cancer, and small-molecule inhibitors have been discovered. This review focuses on summarizing the structural features and biological functions of ATAD2 as well as the existing small-molecule inhibitors targeting ATAD2 for potential cancer therapy.
Review
Biochemistry & Molecular Biology
Susan Costantini, Francesca Capone, Andrea Polo, Palmina Bagnara, Alfredo Budillon
Summary: The review outlines the role of VCP/p97 in different cancers and its potential as a cancer biomarker and therapeutic target, while also addressing the challenges posed by VCP mutations in resistance to inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Jieqiong Wang, Yajie Chen, Canhua Huang, Qian Hao, Shelya X. Zeng, Sara Omari, Yu Zhang, Xiang Zhou, Hua Lu
Summary: Valosin-containing protein (VCP) has been identified as a novel regulator of p53-R273H stability, stabilizing p53-R273H through binding to MDM2 and disrupting its association with mutant p53, while inhibition of VCP leads to ubiquitination and degradation of p53-R273H, promoting cell death. VCP may serve as a potential target for the development of pancreatic cancer therapy.
Article
Multidisciplinary Sciences
Sasa Petrovic, Yvette Roske, Biria Rami, Mai Hoang Quynh Phan, Daniela Panakova, Udo Heinemann
Summary: p97 is a crucial AAA+ ATPase that extracts and unfolds substrate proteins. It contributes to various cellular processes and is regulated by adaptor proteins and posttranslational modifications (PTMs). The crystal structure of a p97:ASPL:METTL21D complex reveals how ASPL enables METTL21D to trimethylate p97 at a deeply buried lysine residue.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Thang Quyet Nguyen, Le Thi My Le, Do Hyeon Kim, Kyung Soo Ko, Hee Taek Lee, Yen Thi Kim Nguyen, Hyoun Sook Kim, Byung Woo Han, Wonchull Kang, Jin Kuk Yang
Summary: The heterodimer of human Ufd1 and human Npl4 is an important cofactor of human p97 ATPase. It plays a crucial role in translocating ubiquitinated proteins from the endoplasmic reticulum membrane to the cytoplasm for degradation.
Article
Biochemistry & Molecular Biology
Johannes Van den Boom, Guendalina Marini, Hemmo Meyer, Helen R. Saibil
Summary: In this study, cryo-EM structures were used to reveal the mechanism of AAA+-ATPase p97 in disassembling a protein phosphatase-1 (PP1) complex. The results showed that PP1 and its associated proteins SDS22 and inhibitor-3 (I3) were tightly loaded onto p97 through direct contact with its N-domain, while the p37 adapter bridged two adjacent p97 N-domains underneath the complex. A portion of I3 was threaded into the central channel of the spiral-shaped p97 hexamer, while the rest remained attached to PP1. These findings elucidate how p97 organizes a protein complex and suggest a hold-and-extract mechanism for p97-mediated disassembly.
Article
Multidisciplinary Sciences
Arjun Saha, Arieh Warshel
Summary: This study explored the molecular basis of substrate translocation by the AAA+ motor of the 26S proteasome using simulation approaches, revealing the role of electrostatic interactions and validating the involvement of bulkier residues in pore loop 1 in substrate translocation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Plant Sciences
Junrui Zhang, Alexandra Vancea, Stefan T. Arold
Summary: This article discusses the lack of research on UBX proteins in plants, and suggests that the AlphaFold algorithm can provide highly accurate protein structure predictions, offering a new approach for research. The combination of cross-kingdom comparison with AF analysis is proposed to inspire and guide experimental research on plant UBX proteins.
TRENDS IN PLANT SCIENCE
(2022)
Article
Neurosciences
Seiji Watanabe, Mai Horiuchi, Yuri Murata, Okiru Komine, Noe Kawade, Akira Sobue, Koji Yamanaka
Summary: Organelle contact sites play a multifunctional role in maintaining cellular homeostasis. This study focuses on the mitochondria-associated membranes (MAM), a site where the endoplasmic reticulum (ER) is connected to the mitochondria, and its involvement in amyotrophic lateral sclerosis (ALS). The researchers found that a protein called ATAD3A, which accumulates at the MAM, is required for MAM maintenance and inhibits mitochondrial fragmentation. Targeting the interaction between sigma-1 receptor (a1R) and ATAD3A could be a promising therapeutic strategy for treating mitochondrial dysfunction in ALS.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Josielle Abrahao, Barbara T. Amaro, Barbara R. Peres, Natalia G. Quel, Annelize Z. B. Araga, Edna G. O. Morea, Maria Isabel N. Cano, Walid A. Houry, Carlos H. I. Ramos
Summary: ATPases from the AAA+ superfamily are crucial for diverse cellular activities, with Rvbs identified as important components in protein complex assembly. This study focused on characterizing Rvbs from Leishmania major, revealing their ATPase activity and expression throughout different life stages. By obtaining specific antibodies against LmRUVBLs, the study provides valuable insights for potential intervention strategies against Leishmaniasis.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Nanoscience & Nanotechnology
Jun Zhou, Peiying Lu, Zixia Liu, Ying Mao, Xiaoliang Hui
Summary: miR-655-3p plays a suppressive role in cell proliferation, migration, and invasion in pancreatic ductal carcinoma (PDAC) by inhibiting the VEGFA/AKT signaling pathway and decreasing the ability of HUVECs to form tubes. miR-655-3p acts as a tumor suppressor in PDAC by targeting the ATAD2-mediated signaling pathway.
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
(2022)
Article
Microbiology
Eric C. DiBiasio, Rebecca A. Dickinson, Catherine E. Trebino, Colby N. Ferreira, Josiah J. Morrison, Jodi L. Camberg
Summary: This study reveals that ZapE is a stress-regulated cell division protein that interacts directly with FtsZ and phospholipids, promoting growth and division after exposure to environmental stress. Deletion of ZapE results in growth delays and a modest division defect, while its interaction with FtsZ suggests a role in ensuring proliferation during and after stress.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell Biology
Haishan Gao, Faxiang Li, Zhejian Ji, Zhubing Shi, Yang Li, Hongtao Yu
Summary: The conserved ATPase p97/Cdc48 mediates cellular processes by unfolding polyubiquitinated proteins. Recent studies have found that p97/Cdc48 can form double hexamers with ordered pore loops, facilitating substrate unfolding and engagement.
Article
Multidisciplinary Sciences
Guimei Yu, Yunpeng Bai, Kunpeng Li, Ovini Amarasinghe, Wen Jiang, Zhong-Yin Zhang
Summary: This study characterized a dodecameric state of VCP and revealed the impact of nucleotide status on the conformation, as well as described a nucleotide status-dependent dodecamerization mechanism. The results highlight new intra- and inter-hexamer conformational changes dictated by nucleotide status, indicating a potential mechanism for controlling VCP oligomeric states.
