Amino-terminal identity of co-existent amyloid and non-amyloid immunoglobulin κ light chain deposits. A human disease to study alterations of protein conformation

Kaplan, Batia; Vidal, Rubén; Kumar, Asok; Ghiso, Jorge; Frangione, Blas; Gallo, Gloria

doi:10.1046/j.1365-2249.1997.4421454.x

Cited by 38 publications

(26 citation statements)

References 15 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, these results show that pressure-induced aggregates were a mixture of amyloid fibrils and amorphous aggregates. Mixed aggregate morphologies have been previously reported for LC deposits found in vivo (28,29).…”

Section: Pressure-induced Equilibrium Unfolding-supporting

confidence: 70%

Kinetics and Energetics of Assembly, Nucleation, and Growth of Aggregates and Fibrils for an Amyloidogenic Protein

Kim¹,

Randolph²,

Stevens³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

The transition states for prenucleation assembly, nucleation, and growth of aggregates and amyloid fibrils were investigated for a dimeric immunoglobulin light chain variable domain, employing pressure, temperature, and solutes as variables. Pressure-induced aggregation was nucleation-dependent and first-order in protein concentration and could be seeded. The insoluble aggregates were mixtures of amyloid fibrils and amorphous aggregates. Activation volumes, activation surface areas, and activation waters of hydration were larger for aggregate growth than for prenucleation assembly or nucleation, although activation free energies were similar for the three processes. Activation free energies for each of the transition states were dominated by the unfavorable free energy of solvation of newly exposed surfaces. Equilibrium dissociation and unfolding of the dimer showed a much larger volume change than those required to form the transition states for the three processes. Thus, the transition states for these steps are similar to the native state, and their formation requires only small structural perturbations. Finally, the presence of Congo red during amyloid fibril formation shortened lag times and caused pressure insensitivity of nucleation, suggesting that this compound or its analogs may not be effective as inhibitors of amyloidosis.

show abstract

Section: Pressure-induced Equilibrium Unfolding-supporting

confidence: 70%

Kinetics and Energetics of Assembly, Nucleation, and Growth of Aggregates and Fibrils for an Amyloidogenic Protein

Kim¹,

Randolph²,

Stevens³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…A few patients have been described in which both types of deposits have been noted. In one such patient, identity of size and amino-terminal sequence has been demonstrated in the L-chain molecules extracted from both types of deposits (Kaplan et al, 1997). In A␤ deposition the diffuse and hard CRϩ, congo red; TTRϩ, transthyretin.…”

Section: Discussionmentioning

confidence: 95%

Amyloid and Nonfibrillar Deposits in Mice Transgenic for Wild-Type Human Transthyretin: A Possible Model for Senile Systemic Amyloidosis

Teng

Yin

Vidal

et al. 2001

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:The human serum protein transthyretin (TTR) is highly fibrillogenic in vitro and is the fibril precursor in both autosomal dominant (familial amyloidotic polyneuropathy [FAP] and familial amyloidotic cardiomyopathy [FAC]) and sporadic (senile systemic amyloidosis [SSA]) forms of human cardiac amyloidosis. We have produced mouse strains transgenic for either wild-type or mutant (TTRLeu55Pro) human TTR genes. Eighty-four percent of C57Bl/6xDBA/2 mice older than 18 months, transgenic for the wild-type human TTR gene, develop TTR deposits that occur primarily in heart and kidney. In most of the animals, the deposits are nonfibrillar and non-Congophilic, but 20% of animals older than 18 months that bear the transgene have human TTR cardiac amyloid deposits identical to the lesions seen in SSA. Amino terminal amino acid sequence analysis and mass spectrometry of the major component extracted from amyloid and nonamyloid deposits revealed that both were intact human TTR monomers with no evidence of proteolysis or codeposition of murine TTR. This is the first instance in which the proteins from amyloid and nonfibrillar deposits in the same or syngeneic animals have been shown to be identical by sequence analysis. It is also the first time in any form of amyloidosis that nonfibrillar deposits have been shown to systematically occur temporally before the appearance of fibrils derived from the same precursor in the same tissues. These findings suggest, but do not prove, that the nonamyloid deposits represent a precursor of the fibril. The differences in the ultrastructure and binding properties of the deposits, despite the identical sizes and amino terminal amino acid sequences of the TTR and the dissociation of deposition and fibril formation, provide evidence that in vivo factors, perhaps associated with aging, impact on both systemic precursor deposition and amyloid fibril formation. (Lab Invest 2001, 81:385-396).

show abstract

“…The presence of protofibril-like fibrils has been reported in immunoglobulin light-chain, 36 A␤, 37 and other types of amyloid proteins such as TTR, in in vitro fibril formation. 38 Depositions of nonfibrillar amyloid protein have been reported in light chain deposition disease, 39 in a Val30Met familial amyloid polyneuropathy patient 40 and in Leu55Pro 41 and normal TTR transgenic mice. 42 Tissue sections from BDF1 mice that were stained with Congo Red showed a distinct apple-green birefringence, and in situ electron microscopy disclosed mature fibril-like components.…”

Section: Senile Amyloidosis Inmentioning

confidence: 99%

Tissue Distribution, Biochemical Properties, and Transmission of Mouse Type A AApoAII Amyloid Fibrils

Korenaga

Xing

et al. 2004

The American Journal of Pathology

View full text Add to dashboard Cite

In mouse strains with the amyloidogenic apolipoprotein A-II (ApoA-II) gene (Apoa2 c ), the type C ApoA-II protein (APOAIIC) associates to form amyloid fibrils AApoAII(C) that lead to development of early onset and systemic amyloidosis with characteristic heavy amyloid deposits in the liver and spleen. We found age-associated heavy deposition of amyloid fibrils [AApoAII(A)] composed of type A ApoA-II protein (APOAIIA) in BDF1 and C57BL/6 mice reared at one of our institutes. AApoAII(A) fibrils were deposited in the intestine, lungs, tongue, and stomach but not in the liver or spleen. AApoAII(A) fibrils were isolated, and morphological, biochemical, and structural characteristics distinct from those seen in AApoAII(C) and mouse AA amyloid fibrils were found. Transmission electron and atomic force microscopy showed that the majority of isolated AApoAII(A) amyloid fibrils featured fine, protofibril-like shapes. AApoAII(A) fibrils have a much weaker affinity for thioflavine T than for AApoAII(C), whereas APOAIIA protein contains less of the ␤-pleated sheet structure than does APOAIIC. The injection of AApoAII(A) fibrils induced amyloid deposition in C57BL/6 and DBA2 mice Amyloidosis is a structural disorder of proteins in which proteins that are normally soluble are deposited in tissues as abnormally ordered, insoluble amyloid fibrils made up of ␤-pleated sheets.

show abstract

Amino-terminal identity of co-existent amyloid and non-amyloid immunoglobulin κ light chain deposits. A human disease to study alterations of protein conformation

Cited by 38 publications

References 15 publications

Kinetics and Energetics of Assembly, Nucleation, and Growth of Aggregates and Fibrils for an Amyloidogenic Protein

Kinetics and Energetics of Assembly, Nucleation, and Growth of Aggregates and Fibrils for an Amyloidogenic Protein

Amyloid and Nonfibrillar Deposits in Mice Transgenic for Wild-Type Human Transthyretin: A Possible Model for Senile Systemic Amyloidosis

Tissue Distribution, Biochemical Properties, and Transmission of Mouse Type A AApoAII Amyloid Fibrils

Contact Info

Product

Resources

About