ArticleStructure (London, England : 1993)2014
Molecular basis of substrate recognition and degradation by human presequence protease.
Article in Structure (London, England : 1993), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 62 citations in OpenAlex.
- Article
- Cross-seeding of IAPP and Aβ42: A review of the molecular link between type 2 diabetes and Alzheimer's disease.Metabolic brain disease · 2025Review
- It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties.Biomolecules · 2025Review
- Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity.bioRxiv : the preprint server for biology · 2025Article
- Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Review
- Inhibition of falcilysin from Plasmodium falciparum by interference with its closed-to-open dynamic transition.Communications biology · 2024Article
- Investigating copy number variants in schizophrenia pedigrees using a new consensus pipeline called PECAN.Scientific reports · 2024Article
- Profiling Protein-Protein Interactions in the Human Brain by Refined Cofractionation Mass Spectrometry.Journal of proteome research · 2024Article
- A cryptic third active site in cyanophycin synthetase creates primers for polymerization.Nature communications · 2022Article
- Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition.Nature communications · 2022Article
- Exploring the Structural Rearrangements of the Human Insulin-Degrading Enzyme through Molecular Dynamics Simulations.International journal of molecular sciences · 2022Article
- In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration.Human genetics · 2021Article
- Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration.Biomedicines · 2021Review
- Structural analysis of Mycobacterium tuberculosis M13 metalloprotease Zmp1 open states.Structure (London, England : 1993) · 2021Article
- Reinvestigating the synthesis and efficacy of small benzimidazole derivatives as presequence protease enhancers.European journal of medicinal chemistry · 2019Article
- Protease-associated import systems are widespread in Gram-negative bacteria.PLoS genetics · 2019Article
- FusC, a member of the M16 protease family acquired by bacteria for iron piracy against plants.PLoS biology · 2018Article
- Bacterial iron acquisition mediated by outer membrane translocation and cleavage of a host protein.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Functional requirement for human pitrilysin metallopeptidase 1 arginine 183, mutated in amyloidogenic neuropathy.Protein science : a publication of the Protein Society · 2018Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human presequence protease (hPreP) is an M16 metalloprotease localized in mitochondria. There, hPreP facilitates proteostasis by utilizing an ∼13,300-Å(3) catalytic chamber to degrade a diverse array of potentially toxic peptides, including mitochondrial presequences and β-amyloid (Aβ), the latter of which contributes to Alzheimer disease pathogenesis. Here, we report crystal structures for hPreP alone and in complex with Aβ, which show that hPreP uses size exclusion and charge complementation for substrate recognition. These structures also reveal hPreP-specific features that permit a diverse array of peptides, with distinct distributions of charged and hydrophobic residues, to be specifically captured, cleaved, and have their amyloidogenic features destroyed. SAXS analysis demonstrates that hPreP in solution exists in dynamic equilibrium between closed and open states, with the former being preferred. Furthermore, Aβ binding induces the closed state and hPreP dimerization. Together, these data reveal the molecular basis for flexible yet specific substrate recognition and degradation by hPreP.
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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.