Solid state NMR assignments of a human λ-III immunoglobulin light chain amyloid fibril.
    
    
        
    
    
        
        Biomol. NMR Assign. 15, 9-16 (2021)
    
    
    
      
      
	
	    The aggregation of antibody light chains is linked to systemic light chain (AL) amyloidosis, a disease where amyloid deposits frequently affect the heart and the kidney. We here investigate fibrils from the lambda-III FOR005 light chain (LC), which is derived from an AL-patient with severe cardiac involvement. In FOR005, five residues are mutated with respect to its closest germline gene segment IGLV3-19 and IGLJ3. All mutations are located close to the complementarity determining regions (CDRs). The sequence segments responsible for the fibril formation are not yet known. We use fibrils extracted from the heart of this particular amyloidosis patient as seeds to prepare fibrils for solid-state NMR. We show that the seeds induce the formation of a specific fibril structure from the biochemically produced protein. We have assigned the fibril core region of the FOR005-derived fibrils and characterized the secondary structure propensity of the observed amino acids. As the primary structure of the aggregated patient protein is different for every AL patient, it is important to study, analyze and report a greater number of light chain sequences associated with AL amyloidosis.
	
	
	    
	
       
      
	
	    
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Scientific Article
    
 
    
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        Keywords
        Al Amyloidosis ; Variable Light Chain Fibrils ; Solid State Nmr; Domain; C-13
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2021
    
 
    
        Prepublished in Year
        2020
    
 
    
        HGF-reported in Year
        2020
    
 
    
    
        ISSN (print) / ISBN
        1874-2718
    
 
    
        e-ISSN
        1874-270X
    
 
    
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	    Volume: 15,  
	    Issue: 1,  
	    Pages: 9-16 
	    Article Number: ,  
	    Supplement: ,  
	
    
 
    
        
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            Springer
        
 
        
            Publishing Place
            Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30203 - Molecular Targets and Therapies
    
 
    
        Research field(s)
        Enabling and Novel Technologies
    
 
    
        PSP Element(s)
        G-503090-001
    
 
    
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        Projekt DEAL
    
 
    
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        Erfassungsdatum
        2020-11-02