PDBsum entry 1jvk

Immune system

PDB id: 1jvk

Contents

Protein chains

216 a.a. *

Waters ×251

* Residue conservation analysis

PDB id:

1jvk

Name:

Immune system

Title:

Three-dimensional structure of an immunoglobulin light chain dimer acting as a lethal amyloid precursor

Structure:

Immunoglobulin lambda light chain. Chain: a, b. Synonym: ig a l. Immunoglobulin lambda-chain. Ig a1 bur

Source:

Homo sapiens. Human. Organism_taxid: 9606

Biol. unit:

Dimer (from PQS)

Resolution:

1.94Å R-factor: 0.223 R-free: 0.254

Authors:

P.C.Bourne,P.A.Ramsland,L.Shan,Z.-C.Fan,C.R.Dewitt,B.B.Shultz, S.S.Terzyan,A.B.Edmundson

Key ref:

P.C.Bourne et al. (2002). Three-dimensional structure of an immunoglobulin light-chain dimer with amyloidogenic properties. Acta Crystallogr D Biol Crystallogr, 58, 815-823. PubMed id: 11976493 DOI: 10.1107/S0907444902004183

Date:

30-Aug-01 Release date: 03-May-02

Protein chains

Q6PJG0  (Q6PJG0_HUMAN) -  Ig-like domain-containing protein from Homo sapiens

Seq: 235 a.a.

Struc: 216 a.a.*

* PDB and UniProt seqs differ at 21 residue positions (black crosses)

DOI no: 10.1107/S0907444902004183

Acta Crystallogr D Biol Crystallogr 58:815-823 (2002)

PubMed id: 11976493

Three-dimensional structure of an immunoglobulin light-chain dimer with amyloidogenic properties.

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.

ABSTRACT

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).

Selected figure(s)

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.]).

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.]).

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2002, 58, 815-823) copyright 2002.

Figures were selected by an automated process.