Three quaternary structures for a single protein.

Huang, De-Bin; Ainsworth, Clinton F.; Stevens, Fred J.; Schiffer, M.

doi:10.1073/pnas.93.14.7017

Cited by 41 publications

(35 citation statements)

References 26 publications

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“…The Ca distribution was also distorted in the C domains, 1.24,~, compared with 0.51 ,~ for the correct structure, though the C domains were in approximately correct positions. The r.m.s, deviation found for the V and C domains in the correct Cle structure is similar to that observed in three different crystal forms of the Loc protein (Huang et al, 1996), determined with 2.3 ,~, resolution data. In another immunoglobulin structure, CD4, the r.m.s.…”

Section: Structure Determination: Molecular Replacementsupporting

confidence: 83%

“…The angle between the local twofold axis of the V domain dimer and the local twofold axis of the C domain dimer defines the 'elbow' bend. The structures of 2I light-chain dimer Loc Schiffer et al, 1989;Huang, Ainsworth, Stevens & Schiffer, 1996) and £II/V light-chain dimer Mcg (Schiffer, Girling, Ely & Edmundson, 1973;Ely, Herron, Harker & Edmundson, 1989) have been previously determined; they were crystallized from several solvents. The Bence-Jones protein from patient Cle was characterized serologically and by its aminoacid sequence as a 211I light chain with Mcg-Kern-Ozconstant region (Eulitz, Murphy, Weiss & Solomon, 1991).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pitfalls of Molecular Replacement: the Structure Determination of an Immunoglobulin Light-Chain Dimer

Huang¹,

Ainsworth²,

Solomon³

et al. 1996

Acta Cryst D

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The structure of protein Cle, a human light-chain dimer from the ,;AII subgroup, was determined using 2.6A data; the R value is 18.4%. The structure was solved, after a false start, by molecular replacement with the ;.II/V Mcg protein as a search structure. When the refinement did not proceed beyond an R value of 27 %, it was discovered that while the constant domains were in their correct positions in the unit cell, the incorrect variable domains were used for defining the molecule. The correct solution required a rotation of 180 around the local twofold axis that relates the two constant domains of the dimer. The correct variable domain positions overlap about 70% of the same volume as the incorrect ones of a symmetry-related molecule. The refinement distorted the geometries of the domains. Though the constant domains were in their correct positions, the r.m.s. (root-mean-square) deviation of the Co~ atom position was 1.2A when the two constant domains were compared. For the correct structure, this value is 0.5 A,. The q9 and ~p angles, the r.m.s, chiral value and the free R value, even when calculated a posteriori, were good indicators of the correctness of the structure. The quaternary structure of the Cle molecule is similar to that in Mcg (crystallized from ammonium sulfate); the elbow bend is 115. However, the arrangement of the variable domains differs from that observed in other variable domain dimers. The variable domains of Cle are 0.7 ,~, closer than in Mcg or variable dimer Rei. The hydrogen bonding at the interface of the two domains is novel. Residues Tyr36 from both monomers form a hydrogen bond that is part of a network with the Gin89 residues from both monomers. For the first time hydrogen bonds were observed between the main-chain peptide N and O atoms of the complementarity-determining region CDR2 and CDR3 segments of both monomers.

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Section: Structure Determination: Molecular Replacementsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Pitfalls of Molecular Replacement: the Structure Determination of an Immunoglobulin Light-Chain Dimer

Huang¹,

Ainsworth²,

Solomon³

et al. 1996

Acta Cryst D

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“…Among the latter were amino-acid residues A28 (Asp), A53 (Val), B53 (Val), A156 (Asp) and B214 (Thr). The first two residues belong to CDR loops 1 and 2 and were also found to be in disallowed regions in the other crystal forms, as well as in other -type light-chain dimers (Furey et al, 1983;Ely et al, 1989;Huang, Ainsworth, Stevens et al, 1996;Terzyan et al, 2003). Torsional strain is possibly the cause of these frequent outliers, since they are involved in tight -type (CDR-1) and -type (CDR-2) turns.…”

Section: P4 3 2 1 2 Crystal Formmentioning

confidence: 93%

“…This angle may vary even among members of a single BJ population. A number of BJ protein structures have been determined using X-ray crystallography, each unique in sequence, antigen specificity, domain dispositions and other detailed features (Epp et al, 1975;Furey et al, 1983;Ely et al, 1989;Huang et al, 1994;Huang, Ainsworth, Solomon et al, 1996;Huang, Ainsworth, Stevens et al, 1996;Roussel et al, 1999;Terzyan et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Bence Jones KWR protein structures determined by X-ray crystallography

Makino

Henschen-Edman

Larson

et al. 2007

Acta Crystallogr D Biol Cryst

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A Bence Jones protein isolated in the early 1960s from a patient (initials KWR) suffering from plasma-cell dyscrasia was crystallized and its structure was analyzed in four different unit cells by X-ray diffraction. The final models of the molecule in all crystal forms were virtually the same, although the elbow angles relating the constant and variable domains of the Bence Jones dimers varied over a range of 10 . The tetragonal form had an R factor of 22.6% and an R free of 28.3% at 2.2 Å resolution. Phosphate or sulfate ions (depending on the crystallization conditions) were found in the antigen-combining sites in all crystals, as well as an unidentified ligand tightly bound in the hydrophobic 'deep pocket' beneath the antigen-binding site. The ligand was treated as a phenol molecule. Two trigonal crystal forms were among those solved. One was grown at pH 4.0 and the other was only obtained after sitting for more than eight months at room temperature. The latter crystal was composed of molecules that were degraded in their constant domains. Both low pH and proteolytic degradation of constant domains are known to promote the polymerization of some Bence Jones proteins into amyloid fibrils. Indeed, in both trigonal crystal forms the molecules are organized with pseudo-hexagonal symmetry about the unique crystallographic axes in a manner suggestive of such fibrils. The arrangement of Bence Jones dimers is also consistent with other observations regarding Bence Jones amyloid-fibril structure and current models. PDB References: Bence Jones KWR protein, P3 1 21, 2omb, r2ombsf; P3 2 21, 2old, r2oldsf; P4 3 2 1 2, 2omn, r2omnsf.

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“…The molecular weight of a Bence-Jones !-type light chain is 22 000±24 000 Da, but these invariably associate to form dimers of twice this weight (Bernier & Putnam, 1963). The structures of a number of BenceJones proteins have been determined by X-ray crystallography (Bourne et al, 2002;Ely et al, 1989;Huang, Ainsworth, Solomon et al, 1996;Huang, Ainsworth, Stevens et al, 1996), each unique in sequence and antigen speci®city and therefore in detailed features. For example, the paired constant domains and the paired variable domains of the dimer are related by an elbow angle, as are the same pairs of domains in an Fab, and this varies among Bence-Jones proteins.…”

Section: Introductionmentioning

confidence: 99%

Four crystal forms of a Bence-Jones protein

2004

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Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40 years ago. Closely related tetragonal and orthorhombic forms belonging to space groups P4 3 2 1 2 and P2 1 2 1 2 1 , with unit-cell parameters a = b = 68.7, c = 182.1 and a = 67.7, b = 69.4, c = 87.3 A Ê , diffract to 1.5 and 1.9 A Ê , respectively. Two closely related trigonal forms, both belonging to space group P3 1 21 with unit-cell parameters a = b = 154.3 A Ê but differing by a doubling of the c axis, one 46.9 A Ê and the other 94.0 A Ê , diffract to 2.9 and 2.6 A Ê resolution, respectively. The trigonal crystal of short c-axis length shows a positive indication of twinning. The trigonal crystal of longer c axis, which appeared only after eight months of incubation at room temperature, is likely to be composed of proteolytically degraded molecules and unlike the other crystal forms contains two entire Bence-Jones dimers in the asymmetric unit. This latter crystal form may shed some light on the formation of ®brils common to certain storage diseases.

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Three quaternary structures for a single protein.

Cited by 41 publications

References 26 publications

Pitfalls of Molecular Replacement: the Structure Determination of an Immunoglobulin Light-Chain Dimer

Pitfalls of Molecular Replacement: the Structure Determination of an Immunoglobulin Light-Chain Dimer

Bence Jones KWR protein structures determined by X-ray crystallography

Four crystal forms of a Bence-Jones protein

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