title: Solid-state NMR chemical shift assignments for AL-09 VLimmunoglobulin light chain fibrils.
abstract: Light chain (AL) amyloidosis is a systemic disease characterized by the formation of immunoglobulin light-chain fibrils in critical organs of the body. The light-chain protein AL-09 presents one severe case of cardiac AL amyloidosis, which contains seven mutations in the variable domain (VL) relative to its germline counterpart, κI O18/O8 VL. Three of these mutations are non-conservative-Y87H, N34I, and K42Q-and previous work has shown that they are responsible for significantly reducing the protein's thermodynamic stability, allowing fibril formation to occur with fast kinetics and across a wide-range of pH conditions. Currently, however, there is extremely limited structural information available which explicitly describes the residues that are involved in supporting the misfolded fibril structure. Here, we assign the site-specific15N and13C chemical shifts of the rigid residues of AL-09 VLfibrils by solid-state NMR, reporting on the regions of the protein involved in the fibril as well as the extent of secondary structure.
authors: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors: Dennis W
authors: DW
authors: Piehl
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
authors: Luis M
authors: LM
authors: Blancas-Mejía
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA. ramirezalvarado.marina@mayo.edu.
authors: Marina
authors: M
authors: Ramirez-Alvarado
authors: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. rienstra@illinois.edu.|Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S Matthews Ave, Urbana, IL, 61801, USA. rienstra@illinois.edu.|Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. rienstra@illinois.edu.
authors: Chad M
authors: CM
authors: Rienstra
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D000072757:Protein Conformation, beta-Strand; D000072417:Protein Domains
chemical_list: D000682:Amyloid; D007147:Immunoglobulin Light Chains
keywords: AL amyloidosis; Light chain fibrils; Protein structure; Solid-state NMR