Solid-state NMR chemical shift assignments for AL-09 VL immunoglobulin 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-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.

journal_name

Biomol NMR Assign

authors

Piehl DW,Blancas-Mejía LM,Ramirez-Alvarado M,Rienstra CM

doi

10.1007/s12104-016-9718-3

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

45-50

issue

1

eissn

1874-2718

issn

1874-270X

pii

10.1007/s12104-016-9718-3

journal_volume

11

pub_type

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