ArticleNature2018
The cryo-electron microscopy structure of huntingtin.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
What it found
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Who cites it
97 citing papers in PubMed, 186 citations in OpenAlex.
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- The HTT1a protein initiates HTT aggregation in a knock-in mouse model of Huntington's disease.Brain : a journal of neurology · 2026Article
- Targeted quantification assays for DNA repair and handling proteins and interactions in Huntington's disease models.bioRxiv : the preprint server for biology · 2026Article
- Huntingtin (HTT) interactome in regulation of DNA repair/remodeling and RNA processing pathways.Life science alliance · 2026Article
- Structural-functional analyses of the huntingtin/HAP40 complex inJournal of biomolecular structure & dynamics · 2026Article
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- High-affinity, structure-validated and selective macrocyclic peptide tools for chemical biology studies of Huntingtin.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Article
- GFP-free live neuron quantitative imaging reveals compartmentalization and growth dynamics of polyQ aggregates.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Luteolin as a dietary flavonoid for brain health: modulating neuroinflammation and cognitive decline in neurodegenerative disorders.Frontiers in nutrition · 2026Review
- Huntington disease: somatic expansion, pathobiology and therapeutics.Nature reviews. Neurology · 2026Review
- Natural products proposed for the management of Huntington's disease (HD): a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization.Science advances · 2025Article
- AI-Enhanced Transcriptomic Discovery of Druggable Targets and Repurposed Therapies for Huntington's Disease.Brain sciences · 2025Review
- Probing How Anti-huntingtin Antibodies Bind the Fibrillar Fuzzy Coat Using Solid-State NMR.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- High-Affinity, Structure-Validated and Selective Macrocyclic Peptide Tools for Chemical Biology Studies of Huntingtin.bioRxiv : the preprint server for biology · 2025Article
- Advances in gene and cellular therapeutic approaches for Huntington's disease.Protein & cell · 2025Review
- Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures.Molecular systems biology · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Huntingtin (HTT) is a large (348 kDa) protein that is essential for embryonic development and is involved in diverse cellular activities such as vesicular transport, endocytosis, autophagy and the regulation of transcription. Although an integrative understanding of the biological functions of HTT is lacking, the large number of identified HTT interactors suggests that it serves as a protein-protein interaction hub. Furthermore, Huntington's disease is caused by a mutation in the HTT gene, resulting in a pathogenic expansion of a polyglutamine repeat at the amino terminus of HTT. However, only limited structural information regarding HTT is currently available. Here we use cryo-electron microscopy to determine the structure of full-length human HTT in a complex with HTT-associated protein 40 (HAP40; encoded by three F8A genes in humans) to an overall resolution of 4 Å. HTT is largely α-helical and consists of three major domains. The amino- and carboxy-terminal domains contain multiple HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats arranged in a solenoid fashion. These domains are connected by a smaller bridge domain containing different types of tandem repeats. HAP40 is also largely α-helical and has a tetratricopeptide repeat-like organization. HAP40 binds in a cleft and contacts the three HTT domains by hydrophobic and electrostatic interactions, thereby stabilizing the conformation of HTT. These data rationalize previous biochemical results and pave the way for improved understanding of the diverse cellular functions of HTT.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.