1bre
IMMUNOGLOBULIN LIGHT CHAIN PROTEIN
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OverviewOverview
An immunoglobulin light chain protein was isolated from the urine of an, individual (BRE) with systemic amyloidosis. Complete amino acid sequence, of the variable region of the light chain (VL) protein established it as a, kappa I, which when compared with other kappa I amyloid associated, proteins had unique residues, including Ile-34, Leu-40, and Tyr-71. To, study the tertiary structure, BRE VL was expressed in Escherichia coli by, using a PCR product amplified from the patient BRE's bone marrow DNA. The, PCR product was ligated into pCZ11, a thermal-inducible replication, vector. Recombinant BRE VL was isolated, purified to homogeneity, and, crystallized by using ammonium sulfate as the precipitant. Two crystal, forms were obtained. In crystal form I the BRE VL kappa domain, crystallizes as a dimer with unit cell constants isomorphous to previously, published kappa protein structures. Comparison with a nonamyloid VL kappa, domain from patient REI, identified significant differences in position of, residues in the hypervariable segments plus variations in framework region, (FR) segments 40-46 (FR2) and 66-67 (FR3). In addition, positional, differences can be seen along the two types of local diads, corresponding, to the monomer-monomer and dimer-dimer interfaces. From the packing, diagram, a model for the amyloid light chain (AL) fibril is proposed based, on a pseudohexagonal spiral structure with a rise of approximately the, width of two dimers per 360 degree turn. This spiral structure could be, consistent with the dimensions of amyloid fibrils as determined by, electron microscopy.
About this StructureAbout this Structure
1BRE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Tertiary structure of an amyloid immunoglobulin light chain protein: a proposed model for amyloid fibril formation., Schormann N, Murrell JR, Liepnieks JJ, Benson MD, Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9490-4. PMID:7568160
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