Solid-state NMR chemical shift assignments for AL-09 VL immunoglobulin light chain fibrils

Dennis W. Piehl, Luis M. Blancas-Mejía, Marina Ramirez-Alvarado, Chad M. Rienstra

Research output: Contribution to journalArticle

8 Scopus citations

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-specific 15N and 13C chemical shifts of the rigid residues of AL-09 VL fibrils by solid-state NMR, reporting on the regions of the protein involved in the fibril as well as the extent of secondary structure.

Original languageEnglish (US)
Pages (from-to)45-50
Number of pages6
JournalBiomolecular NMR Assignments
Volume11
Issue number1
DOIs
StatePublished - Apr 1 2017

Keywords

  • AL amyloidosis
  • Light chain fibrils
  • Protein structure
  • Solid-state NMR

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry

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