Upon DNA damage, the ALC1/CHD1L nucleosome remodeling enzyme (remodeler) is activated by binding to poly(ADP-ribose). How activated ALC1 recognizes the nucleosome, as well as how this recognition is coupled to remodeling, is unknown. Here, we show that remodeling by ALC1 requires a wild-type acidic patch on the entry side of the nucleosome. The cryo-electron microscopy structure of a nucleosome-ALC1 linker complex reveals a regulatory linker segment that binds to the acidic patch. Mutations within this interface alter the dynamics of ALC1 recruitment to DNA damage and impede the ATPase and remodeling activities of ALC1. Full activation requires acidic patch-linker segment interactions that tether the remodeler to the nucleosome and couple ATP hydrolysis to nucleosome mobilization. Upon DNA damage, such a requirement may be used to modulate ALC1 activity via changes in the nucleosome acidic patches.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116876 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2020.108529 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of Lauric Acid as a Potent Sodium Channel Na1.5 Blocker from Compound Chinese Medicine Wenxin Keli.
Drug Des Devel Ther
January 2025
State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People's Republic of China.
Purpose: The major cardiac voltage-gated sodium channel Na1.5 (I) is essential for cardiac action potential initiation and subsequent propagation. Compound Chinese medicine Wenxin Keli (WXKL) has been shown to suppress arrhythmias and heart failure.
View Article and Find Full Text PDFCryo-EM structure of an activated GPR4-Gs signaling complex.
Nat Commun
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Article Synopsis
- G protein-coupled receptor 4 (GPR4) is part of a group called proton-sensing GPCRs that respond to pH changes and regulate various physiological functions, with its overactivation noted in acidic tumor environments.
- Researchers used cryo-electron microscopy to determine the 3D structures of zebrafish GPR4 at different pH levels, revealing important histidine and acidic residues that affect its proton-sensing ability, alongside key triad residues.
- The study also identified a cluster of aromatic residues in GPR4's orthosteric pocket that may play a crucial role in transferring signals to the inside of the cell, laying the groundwork for further research on psGPCRs.
Roles of Mature Domain Targeting Signals (MTSs) for Protein Translocation and Secretion in .
Int J Mol Sci
December 2024
Institute of Food Technology, Department of Food Science and Technology, BOKU University, 1190 Vienna, Austria.
is a potential bacterial cell factory to develop delivery systems for vaccines and therapeutic proteins. Much progress has been made in applications using engineered against, e.g.
View Article and Find Full Text PDFAssessing the role of Berberine as an inhibitor of advanced glycation end products (AGEs) formation using in vitro and molecular interaction studies.
Arch Biochem Biophys
January 2025
Department of Biochemistry, J.N.M.C., Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, U.P., India. Electronic address:
Glycation and aggregation of proteins have garnered more interest in recent years. Glycation leads to the formation of protein aggregates and advanced glycation ends (AGEs) that play crucial roles within several pathological conditions. The objective of our study is to gain a deeper understanding of the formation of AGEs and aggregates of human serum albumin (HSA) in the presence of methylglyoxal and the protective effects of the phytochemical berberine.
View Article and Find Full Text PDFThe CLCA1/TMEM16A/Cl- current axis associates with H2S deficiency in diabetic kidney injury.
JCI Insight
January 2025
Center for Precision Medicine, Department of Medicine, and.
The role played by anionic channels in diabetic kidney disease (DKD) is not known. Chloride channel accessory 1 (CLCA1) facilitates the activity of TMEM16A (Anoctamin-1), a Ca2+-dependent Cl- channel. We examined if CLCA1/TMEM16A had a role in DKD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!