Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:Q16637 (
SMA
)
8,107
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In an attempt to understand the mechanism of amyloid fibril formation in light chain amyloidosis, the properties of amyloidogenic (
SMA
) and benign (LEN) immunoglobulin light chain variable domains (VL) were compared. The conformations of LEN and
SMA
were measured using secondary and tertiary structural probes over the pH range from 2 and 8. At all pH values, LEN was more stable than
SMA
. The CD spectra of LEN at pH 2 were comparable to those of
SMA
at pH 7.5, indicating that the low pH conformation of LEN closely resembles that of
SMA
at physiological pH. At low pH, a relatively unfolded intermediate conformation is populated for
SMA
and rapidly leads to amyloid fibrils. The lack of such an intermediate with LEN, is attributed to sequence differences and accounts for the lack of LEN fibrils in the absence of
agitation
. A kappa IV-specific monoclonal antibody that recognizes the N-terminal of
SMA
caused unraveling of the fibrils to the protofilaments and was observed to bind to one end of
SMA
protofilaments by atomic force microscopy. The antibody result indicates that each protofilament is asymmetric with different ends. A model for the formation of fibrils by
SMA
is proposed.
...
PMID:A model for amyloid fibril formation in immunoglobulin light chains based on comparison of amyloidogenic and benign proteins and specific antibody binding. 1296 17
