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PDBsum entry 1jvk
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Immune system
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PDB id
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1jvk
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure of an immunoglobulin light-Chain dimer with amyloidogenic properties.
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Authors
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P.C.Bourne,
P.A.Ramsland,
L.Shan,
Z.C.Fan,
C.R.Dewitt,
B.B.Shultz,
S.S.Terzyan,
C.R.Moomaw,
C.A.Slaughter,
L.W.Guddat,
A.B.Edmundson.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2002,
58,
815-823.
[DOI no: ]
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PubMed id
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Abstract
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The X-ray structure of an immunoglobulin light-chain dimer isolated from the
urine as a "Bence-Jones protein" from a patient with multiple myeloma
and amyloidosis (Sea) was determined at 1.94 A resolution and refined to R and
R(free) factors of 0.22 and 0.25, respectively. This "amyloidogenic"
protein crystallized in the orthorhombic P2(1)2(1)2(1) space group with
unit-cell parameters a = 48.28, b = 83.32, c = 112.59 A as determined at 100 K.
In the vital organs (heart and kidneys), the equivalent of the urinary protein
produced fibrillar amyloid deposits which were fatal to the patient. Compared
with the amyloidogenic Mcg light-chain dimer, the Sea protein was highly soluble
in aqueous solutions and only crystallized at concentrations approaching 100 mg
ml(-1). Both the Sea and Mcg proteins packed into crystals in highly ordered
arrangements typical of strongly diffracting crystals of immunoglobulin
fragments. Overall similarities and significant differences in the
three-dimensional structures and crystalline properties are discussed for the
Sea and Mcg Bence-Jones proteins, which together provide a generalized model of
abnormalities present in lambda chains, facilitating a better understanding of
amyloidosis of light-chain origin (AL).
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Figure 5.
Figure 5 Comparison of the CDR3s of the Sea and Mcg Bence-Jones
dimers, presented as stereo diagrams. Components of monomer B
(H-chain analogs) are colored magenta and segments of monomer A
(L chains) are yellow. CDR3 loops act as pillars of the active
sites and their relative locations in each dimer largely
determine the magnitudes of the openings into the binding
cavities. This opening is significantly narrower in the Sea
dimer (8 versus 15 Å), but the depths are practically the same.
The phenylalanine residues at the lower ends mark the floors of
the cavities. This figure was prepared with the program
MOLSCRIPT (Kraulis, 1991[Kraulis, P. J. (1991). J. Appl. Cryst.
24, 946-950.]).
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Figure 6.
Figure 6 Stereo diagrams of the CDR1 and CDR3 loops in the two
conformational isomers of the Sea dimer. CDR1 is yellow in
monomer A (L-type isomer) and blue in monomer B (H-chain
analog). CDR3 is magenta in monomer A and red in monomer B.
Hydrogen bonds between CDR1 and CDR3 are designated by dotted
lines and the interatomic distances in Å between backbone
carbonyl and amide groups are superimposed. Short stretches of
antiparallel  -strand
pairing occur between the descending arm of the CDR1 loop and
the ascending arm of CDR3 in both monomers. Otherwise, the
conformations of the CDR1 and CDR3 loops are substantially
different in the two isomers. The models were drawn with the
program MOLSCRIPT (Kraulis, 1991[Kraulis, P. J. (1991). J. Appl.
Cryst. 24, 946-950.]).
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2002,
58,
815-823)
copyright 2002.
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