6SM1
Wild type immunoglobulin light chain (WT-1)
Summary for 6SM1
| Entry DOI | 10.2210/pdb6sm1/pdb |
| Related | 4nki |
| Descriptor | Immunoglobulin lambda variable 2-14, CALCIUM ION, DI(HYDROXYETHYL)ETHER, ... (5 entities in total) |
| Functional Keywords | al amyloidosis, antibody folding, protein stability, dynamics, immune system |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 12371.54 |
| Authors | Kazman, P.,Vielberg, M.-T.,Cendales, M.D.P.,Hunziger, L.,Weber, B.,Hegenbart, U.,Zacharias, M.,Koehler, R.,Schoenland, S.,Groll, M.,Buchner, J. (deposition date: 2019-08-21, release date: 2020-03-18, Last modification date: 2024-01-24) |
| Primary citation | Kazman, P.,Vielberg, M.T.,Pulido Cendales, M.D.,Hunziger, L.,Weber, B.,Hegenbart, U.,Zacharias, M.,Kohler, R.,Schonland, S.,Groll, M.,Buchner, J. Fatal amyloid formation in a patient's antibody light chain is caused by a single point mutation. Elife, 9:-, 2020 Cited by PubMed Abstract: In systemic light chain amyloidosis, an overexpressed antibody light chain (LC) forms fibrils which deposit in organs and cause their failure. While it is well-established that mutations in the LC's V domain are important prerequisites, the mechanisms which render a patient LC amyloidogenic are ill-defined. In this study, we performed an in-depth analysis of the factors and mutations responsible for the pathogenic transformation of a patient-derived λ LC, by recombinantly expressing variants in . We show that proteolytic cleavage of the patient LC resulting in an isolated V domain is essential for fibril formation. Out of 11 mutations in the patient V, only one, a leucine to valine mutation, is responsible for fibril formation. It disrupts a hydrophobic network rendering the C-terminal segment of V more dynamic and decreasing domain stability. Thus, the combination of proteolytic cleavage and the destabilizing mutation trigger conformational changes that turn the LC pathogenic. PubMed: 32151314DOI: 10.7554/eLife.52300 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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