人免疫球蛋白κIV轻链可变结构域LEN的主链和侧链（1）H、（13）C和（15）N共振归属

Backbone and side-chain (1)H, (13)C and (15)N resonance assignments of LEN, a human immunoglobulin kappaIV light-chain variable domain.

作者信息

Mukherjee Sujoy, Pondaven Simon P, Höfer Nicole, Jaroniec Christopher P

机构信息

Department of Chemistry, The Ohio State University, Columbus, OH 43210, USA.

出版信息

Biomol NMR Assign. 2009 Dec;3(2):255-9. doi: 10.1007/s12104-009-9188-y.

DOI:10.1007/s12104-009-9188-y

PMID:19768664

Abstract

(1)H, (13)C and (15)N resonance assignments are presented for a recombinant 114 amino acid human immunoglobulin (Ig) kappaIV light-chain variable domain (VL) LEN, which displays a high degree of sequence identity with another human Ig kappaIV VL, SMA. While SMA is highly amyloidogenic in vivo and in vitro and has been linked to the pathogenesis of light-chain amyloidosis, LEN is non-amyloidogenic in vivo and can be converted to the amyloid state only in vitro under destabilizing conditions. Measurements of longitudinal and transverse amide (15)N relaxation rates confirm that, as expected, LEN is a dimer at physiological pH and typical concentrations used for NMR studies, and the analysis of secondary chemical shifts indicates that the protein has a high beta-sheet content. These findings are consistent with previously published biophysical data and the high-resolution X-ray structure of LEN.

摘要

本文给出了重组的114个氨基酸的人免疫球蛋白（Ig）κIV轻链可变区（VL）LEN的氢（¹H）、碳（¹³C）和氮（¹⁵N）共振归属。LEN与另一种人IgκIV VL，即SMA，具有高度的序列同一性。虽然SMA在体内和体外都具有高度的淀粉样变性，并且与轻链淀粉样变性的发病机制有关，但LEN在体内不具有淀粉样变性，只有在不稳定条件下体外才能转化为淀粉样状态。纵向和横向酰胺¹⁵N弛豫率的测量证实，正如预期的那样，LEN在生理pH值和用于核磁共振研究的典型浓度下是二聚体，二级化学位移分析表明该蛋白质具有高β-折叠含量。这些发现与之前发表的生物物理数据以及LEN的高分辨率X射线结构一致。