7NSL

AL amyloid fibril from a lambda 1 light chain

Summary for 7NSL

• Entry DOI: 10.2210/pdb7nsl/pdb
• EMDB information: 12570
• Descriptor: Amyloid lambda1 light chain (1 entity in total)
• Functional Keywords: amyloid, antibody, systemic amyloidosis, light chain, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 7
• Total formula weight: 84856.48

Authors

Karimi Farsijani, S.,Radamaker, L.,Fandrich, M. (deposition date: 2021-03-08, release date: 2021-11-24, Last modification date: 2024-10-23)

Primary citation

Radamaker, L.,Karimi-Farsijani, S.,Andreotti, G.,Baur, J.,Neumann, M.,Schreiner, S.,Berghaus, N.,Motika, R.,Haupt, C.,Walther, P.,Schmidt, V.,Huhn, S.,Hegenbart, U.,Schonland, S.O.,Wiese, S.,Read, C.,Schmidt, M.,Fandrich, M.
Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM.
Nat Commun, 12:6434-6434, 2021

PubMed Abstract: Systemic AL amyloidosis is a rare disease that is caused by the misfolding of immunoglobulin light chains (LCs). Potential drivers of amyloid formation in this disease are post-translational modifications (PTMs) and the mutational changes that are inserted into the LCs by somatic hypermutation. Here we present the cryo electron microscopy (cryo-EM) structure of an ex vivo λ1-AL amyloid fibril whose deposits disrupt the ordered cardiomyocyte structure in the heart. The fibril protein contains six mutational changes compared to the germ line and three PTMs (disulfide bond, N-glycosylation and pyroglutamylation). Our data imply that the disulfide bond, glycosylation and mutational changes contribute to determining the fibril protein fold and help to generate a fibril morphology that is able to withstand proteolytic degradation inside the body.

PubMed: 34741031
DOI: 10.1038/s41467-021-26553-9

Experimental method

ELECTRON MICROSCOPY (3.1 Å)