The complete amino acid sequence of a prototype immunoglobulin-λ light-chain-type amyloid-fibril protein AR

Sletten, Knut; Natvig, J. B.; Husby, Gunnar; Juul, Jessie

doi:10.1042/bj1950561

Cited by 78 publications

(66 citation statements)

References 18 publications

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“…Amino acid analysis of proteins was performed as described [15], on a Biotronic (Frankfurt am Main, Germany) Automatic Amino Acid Analyser LC 5000.…”

Section: Methodsmentioning

confidence: 99%

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Constant Region of a κ III Immunoglobulin Light Chain as a Major AL‐Amyloid Protein

et al. 1998

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Engvig JP, Olsen KE, Gislefoss RE, Sletten K, Wahlström O, Westermark P. Constant Region of a k III Immunoglobulin Light Chain as a Major AL-Amyloid Protein. Scand J Immunol 1998;48:92-98 AL-amyloidoses are generally described as a group of disorders in which N-terminal fragments of monoclonal immunoglobulin light chains are transferred into amyloid fibrils. We have, by amino acid sequence analyses and immunological methods, characterized the Bence-Jones protein and the corresponding AL protein as a k III immunoglobulin light chain from material of a patient with systemic AL-amyloidosis presenting as a local inguinal tumour. The two proteins showed some unique features. The major part of the AL amyloid fibril protein consisted of C-terminal fragments of the Bence-Jones protein. Furthermore, both the Bence-Jones protein and the AL protein were glycosylated, with possibly a glycosylation in the constant part of the light chain.

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“…Amino acid analysis of proteins was performed as described [15], on a Biotronic (Frankfurt am Main, Germany) Automatic Amino Acid Analyser LC 5000.…”

Section: Methodsmentioning

confidence: 99%

“…The whole amyloid-laden tissue mass was used for amyloid fibril extraction as described, [13] with the small modification that the amyloid-rich bottom material was also used. Protein fractions were alkylated with 4-vinyl-pyridine (for AL-VAG) as described [14], or iodo-acetic acid (for BJ-VAG) as described [15].…”

Section: Methodsmentioning

confidence: 99%

Constant Region of a κ III Immunoglobulin Light Chain as a Major AL‐Amyloid Protein

et al. 1998

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“…Also, the ratio between l and k light chains is 2:1 for those associated with amyloidosis, whereas a ratio of 1:2 is observed in myelomatosis and also in normal plasma [3]. Moreover, subgroup VI of the l chains is particularly associated with AL amyloidosis [4,5]. The immunoglobulin light chains therefore provide a unique tool for studying the role of amino acid sequence of proteins involved in amyloid formation.…”

Section: Introductionmentioning

confidence: 99%

A Glycosylated Bence Jones Protein and its Autologous Amyloid Light Chain Containing Potentially Amyloidogenic Residues

et al. 1998

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Amyloidosis is characterized by deposition of protein fibrils in various tissues. The wide variety of sequences of both amyloidogenic and non‐amyloidogenic immunoglobulin light chains makes them a unique tool for addressing the importance of primary structure in the formation of insoluble fibrils. In this study, we have determined the primary structure of the κ I immunoglobulin light chain from both the urinary Bence Jones protein and the deposited amyloid fibrils of a patient (MH) with primary amyloidosis. The sequence identity of urinary‐excreted and tissue‐deposited light chains excluded biclonality and somatic mutations and confirmed that the light chain existed in both a soluble and an insoluble form. Several residues have been previously reported to be significantly associated with amyloidogenic κ chains. Many of these were found in the MH sequence, including Asp31, Asn45, Phe49, Gln55, His70, Asn/Gly93 and Pro/Val96, thereby supporting their potential role in fibrillogenesis. In addition, Asn20 and Pro60 of protein MH replaced the normally conserved Thr20 and Ser60. Asn20 was glycosylated in both the Bence Jones and the amyloid fibril protein MH. Cumulative effects of amyloid‐associated residues and glycosylation might have rendered the immunoglobulin light chain MH prone to fibril formation.

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“…Apo CII was digested with trypsin and the peptides were purified by gel filtration and by thin-layer chromatography [50]. Automatic amino acid sequence analyses were made on a JEOL-47K sequence analyzer [50] and on an Applied Biosystems Inc. 477A Pulsed Liquid Phase sequencer with an online PTH 120A Analyzer. Sequencing was performed with regular cycle programs and chemicals from the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

“…For amino acid analyses, peptides were hydrolyzed in 6 M HCl for 24 h at 108 -110 "C and the hydrolysate analyzed on a Biotronik LC 5000 automatic amino acid analyzer [50]. Apo CII was digested with trypsin and the peptides were purified by gel filtration and by thin-layer chromatography [50].…”

Section: Methodsmentioning

confidence: 99%

Primary structure of the bovine analogues to human apolipoproteins CII and CIII

Bengtsson‐Olivecrona

Sletten

1990

European Journal of Biochemistry

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Two major isoforms of the bovine analogue to human apolipoprotein (apo) CII were purified from plasma. They were both as effective as human apo CII in activating lipoprotein lipase. Amino acid sequencing revealed that one form contained 79 amino acid residues, and corresponded to human pro apo CII. The other form lacked the first six residues at its N-terminus. This was apparently due to cleavage of the -Gln-Asp-linkage in the sequence H2N-Ala-His-Val-Pro-Gln-Gln-Asp-Glu-, analogous to cleavages described for human apo A1 and apo CII.Previous studies with human apo CII have shown that the ability to activate lipoprotein lipase resides in the C-terminal third of the molecule. This was highly conserved in the bovine analogue: of the 30 last residues, 21 are identical. Five residues in this part of human apo CII have been reported to be essential for activation of lipoprotein lipase. Only one of these, Tyr63, is present in the bovine sequence. The bovine structure contains a threonine at position 61, instead of serine in the human, and the four last residues are -Ser-Gly-Lys-Asp instead of the allegedly necessary -Lys-Gly-Glu-Glu. Three differently sialylated isoforms of the bovine analogue to human apolipoprotein CIII were also isolated and partially sequenced. All three lacked the first three N-terminal residues as compared to sequences from other species (man, dog and rat). Sequence differences were more pronounced at the ends than in the central parts of the apo CIII molecules.Transport of triacylglycerol in lipoproteins is a major pathway for energy transfer between tissues. Triacylglycerol-rich lipoproteins are formed in the intestine (chylomicra) and in the liver (very-low-density-lipoproteins). Their metabolism involves two major steps. Most of the triacylglycerols are unloaded by lipoprotein lipase at the vascular endothelium in peripheral tissues [ 11. The resulting remnant lipoproteins are then removed from the circulation mainly by the liver [2 -41. Apolipoproteins (apo) CII and CHI appear to be involved in the regulation of both steps. These proteins have flexible conformations [5] that allow them to bind reversibly to lipid/ water interfaces and to transfer rapidly between lipoprotein particles. When triacylglycerol-rich lipoproteins enter plasma they take up apo CII and CHI; when the particles are degraded by lipoprotein lipase the C apolipoproteins transfer back to other lipoproteins [6, 71. For hydrolysis by lipoprotein lipase the lipoproteins must carry apo CII, an activator for the enzyme [8, 91. In the absence of apo CII, triacylglycerol transport is severely impeded and gross hypertriglyceridemia ensues [lo]. Apo CIII has been shown to impede the interaction of lipoproteins with the remnant receptor, thus preventing their uptake by the liver until the lipase reaction has reduced them sufficiently in size so that most of the C apoproteins have been shed from the particles [4,11, 121. In addition, apo CIII has been shown to inhibit the action of lipoprotein lipase and the Human apo CII is a 79-a...

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The complete amino acid sequence of a prototype immunoglobulin-λ light-chain-type amyloid-fibril protein AR

Cited by 78 publications

References 18 publications

Constant Region of a κ III Immunoglobulin Light Chain as a Major AL‐Amyloid Protein

Constant Region of a κ III Immunoglobulin Light Chain as a Major AL‐Amyloid Protein

A Glycosylated Bence Jones Protein and its Autologous Amyloid Light Chain Containing Potentially Amyloidogenic Residues

Primary structure of the bovine analogues to human apolipoproteins CII and CIII

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