13 Result(s)
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Lukasz A. Joachimiak
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Article
Open AccessHairpin trimer transition state of amyloid fibril
Protein fibril self-assembly is a universal transition implicated in neurodegenerative diseases. Although fibril structure/growth are well characterized, fibril nucleation is poorly understood. Here, we use a ...
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Article
Open AccessDual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin
The Papain-like protease (PLpro) is a domain of a multi-functional, non-structural protein 3 of coronaviruses. PLpro cleaves viral polyproteins and posttranslational conjugates with poly-ubiquitin and protecti...
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Article
Open AccessFTD-tau S320F mutation stabilizes local structure and allosterically promotes amyloid motif-dependent aggregation
Amyloid deposition of the microtubule-associated protein tau is associated with neurodegenerative diseases. In frontotemporal dementia with abnormal tau (FTD-tau), missense mutations in tau enhance its aggrega...
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Article
Open AccessNetwork of hotspot interactions cluster tau amyloid folds
Cryogenic electron microscopy has revealed unprecedented molecular insight into the conformations of β-sheet-rich protein amyloids linked to neurodegenerative diseases. It remains unknown how a protein can ado...
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Protocol
Cross-Linking Mass Spectrometry Analysis of Metastable Compact Structures in Intrinsically Disordered Proteins
Protein assembly into beta-sheet-rich amyloids is a common phenomenon in neurodegenerative diseases including Alzheimer’s (AD) and Parkinson’s (PD). The proteins implicated in amyloid deposition are often intr...
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Protocol
Modifying Amyloid Motif Aggregation Through Local Structure
Protein assembly into β-sheet-rich amyloid structures is a general biophysical phenomenon that has significant biological consequences, most notable for their prominent association with neurodegenerative disea...
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Article
Open AccessDnaJC7 binds natively folded structural elements in tau to inhibit amyloid formation
Molecular chaperones, including Hsp70/J-domain protein (JDP) families, play central roles in binding substrates to prevent their aggregation. How JDPs select different conformations of substrates remains poorl...
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Article
Open AccessTau strains shape disease
Tauopathies consist of over 25 different neurodegenerative diseases that include argyrophilic grain disease (AGD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick’s disease (PiD...
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Article
Open AccessBiophysical properties of a tau seed
Pathogenesis of tauopathies involves conversion of tau monomer into pathological tau conformers that serve as templates to recruit native tau into growing assemblies. Small soluble tau seeds have been proposed...
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Article
Open AccessRegulatory inter-domain interactions influence Hsp70 recruitment to the DnaJB8 chaperone
The Hsp40/Hsp70 chaperone families combine versatile folding capacity with high substrate specificity, which is mainly facilitated by Hsp40s. The structure and function of many Hsp40s remain poorly understood,...
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Article
Open AccessTau local structure shields an amyloid-forming motif and controls aggregation propensity
Tauopathies are neurodegenerative diseases characterized by intracellular amyloid deposits of tau protein. Missense mutations in the tau gene (MAPT) correlate with aggregation propensity and cause dominantly inhe...
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Article
xTract: software for characterizing conformational changes of protein complexes by quantitative cross-linking mass spectrometry
Chemical cross-linking in combination with mass spectrometry generates distance restraints of amino acid pairs in close proximity on the surface of native proteins and protein complexes. In this study we used ...
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Article
Computational redesign of protein-protein interaction specificity
We developed a 'computational second-site suppressor' strategy to redesign specificity at a protein-protein interface and applied it to create new specifically interacting DNase-inhibitor protein pairs. We dem...
