Seeded fibrils of the germline variant of human λ-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability
Systemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we studied the fibril structure of a recombinant light chain fragment...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
October 22, 2020
|
| In: |
The journal of biological chemistry
Year: 2020, Volume: 295, Issue: 52, Pages: 18474-18484 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.RA120.016006 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.RA120.016006 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0021925817507139 
|
| Author Notes: | Tejaswini Pradhan, Karthikeyan Annamalai, Riddhiman Sarkar, Stefanie Huhn, Ute Hegenbart, Stefan Schönland, Marcus Fändrich, and Bernd Reif |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1747378941 | ||
| 003 | DE-627 | ||
| 005 | 20230426111145.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210204s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1074/jbc.RA120.016006 |2 doi | |
| 035 | |a (DE-627)1747378941 | ||
| 035 | |a (DE-599)KXP1747378941 | ||
| 035 | |a (OCoLC)1341390204 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Pradhan, Tejaswini |e VerfasserIn |0 (DE-588)1226311784 |0 (DE-627)1747381667 |4 aut | |
| 245 | 1 | 0 | |a Seeded fibrils of the germline variant of human λ-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability |c Tejaswini Pradhan, Karthikeyan Annamalai, Riddhiman Sarkar, Stefanie Huhn, Ute Hegenbart, Stefan Schönland, Marcus Fändrich, and Bernd Reif |
| 246 | 3 | 3 | |a Seeded fibrils of the germline variant of human lambda-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability |
| 264 | 1 | |c October 22, 2020 | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 04.02.2021 | ||
| 520 | |a Systemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we studied the fibril structure of a recombinant light chain fragment corresponding to the fibril protein from patient FOR005, together with fibrils formed by protein sequence variants that are derived from the closest germline (GL) sequence. Both analyzed fibril structures were seeded with ex-vivo amyloid fibrils purified from the explanted heart of this patient. We find that residues 11-42 and 69-102 adopt β-sheet conformation in patient protein fibrils. We identify arginine-49 as a key residue that forms a salt bridge to aspartate-25 in the patient protein fibril structure. In the germline sequence, this residue is replaced by a glycine. Fibrils from the GL protein and from the patient protein harboring the single point mutation R49G can be both heterologously seeded using patient ex-vivo fibrils. Seeded R49G fibrils show an increased heterogeneity in the C-terminal residues 80-102, which is reflected by the disappearance of all resonances of these residues. By contrast, residues 11-42 and 69-77, which are visible in the MAS solid-state NMR spectra, show 13Cα chemical shifts that are highly like patient fibrils. The mutation R49G thus induces a conformational heterogeneity at the C terminus in the fibril state, whereas the overall fibril topology is retained. These findings imply that patient mutations in FOR005 can stabilize the fibril structure. | ||
| 650 | 4 | |a AL amyloidosis · antibody light chain · protein aggregation · fibril seeding · Magic Angle Spinning (MAS) solid-state NMR spectroscopy | |
| 650 | 4 | |a amyloid | |
| 650 | 4 | |a antibody | |
| 650 | 4 | |a nuclear magnetic resonance (NMR) | |
| 650 | 4 | |a protein aggregation | |
| 650 | 4 | |a solid state NMR | |
| 700 | 1 | |a Annamalai, Karthikeyan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sarkar, Riddhiman |e VerfasserIn |4 aut | |
| 700 | 1 | |a Huhn, Stefanie |d 1982- |e VerfasserIn |0 (DE-588)1014984424 |0 (DE-627)705313190 |0 (DE-576)349876436 |4 aut | |
| 700 | 1 | |a Hegenbart, Ute |e VerfasserIn |0 (DE-588)1028373708 |0 (DE-627)73062157X |0 (DE-576)35901903X |4 aut | |
| 700 | 1 | |a Schönland, Stefan |d 1969- |e VerfasserIn |0 (DE-588)122405226 |0 (DE-627)705896137 |0 (DE-576)293255792 |4 aut | |
| 700 | 1 | |a Fändrich, Marcus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Reif, Bernd |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journal of biological chemistry |d [Amsterdam] : Elsevier B.V., 1905 |g 295(2020), 52, Seite 18474-18484 |h Online-Ressource |w (DE-627)269247025 |w (DE-600)1474604-9 |w (DE-576)077883837 |x 1083-351X |7 nnas |a Seeded fibrils of the germline variant of human λ-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability |
| 773 | 1 | 8 | |g volume:295 |g year:2020 |g number:52 |g pages:18474-18484 |g extent:11 |a Seeded fibrils of the germline variant of human λ-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability |
| 856 | 4 | 0 | |u https://doi.org/10.1074/jbc.RA120.016006 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S0021925817507139 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20210204 | ||
| 993 | |a Article | ||
| 994 | |a 2020 | ||
| 998 | |g 122405226 |a Schönland, Stefan |m 122405226:Schönland, Stefan |d 910000 |d 910100 |d 50000 |e 910000PS122405226 |e 910100PS122405226 |e 50000PS122405226 |k 0/910000/ |k 1/910000/910100/ |k 0/50000/ |p 6 | ||
| 998 | |g 1028373708 |a Hegenbart, Ute |m 1028373708:Hegenbart, Ute |d 910000 |d 910100 |d 50000 |e 910000PH1028373708 |e 910100PH1028373708 |e 50000PH1028373708 |k 0/910000/ |k 1/910000/910100/ |k 0/50000/ |p 5 | ||
| 998 | |g 1014984424 |a Huhn, Stefanie |m 1014984424:Huhn, Stefanie |d 910000 |d 910100 |e 910000PH1014984424 |e 910100PH1014984424 |k 0/910000/ |k 1/910000/910100/ |p 4 | ||
| 999 | |a KXP-PPN1747378941 |e 3848535939 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"family":"Pradhan","display":"Pradhan, Tejaswini","role":"aut","given":"Tejaswini"},{"role":"aut","given":"Karthikeyan","display":"Annamalai, Karthikeyan","family":"Annamalai"},{"given":"Riddhiman","role":"aut","family":"Sarkar","display":"Sarkar, Riddhiman"},{"display":"Huhn, Stefanie","family":"Huhn","given":"Stefanie","role":"aut"},{"family":"Hegenbart","display":"Hegenbart, Ute","role":"aut","given":"Ute"},{"family":"Schönland","display":"Schönland, Stefan","role":"aut","given":"Stefan"},{"role":"aut","given":"Marcus","display":"Fändrich, Marcus","family":"Fändrich"},{"given":"Bernd","role":"aut","display":"Reif, Bernd","family":"Reif"}],"language":["eng"],"titleAlt":[{"title":"Seeded fibrils of the germline variant of human lambda-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability"}],"title":[{"title":"Seeded fibrils of the germline variant of human λ-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability","title_sort":"Seeded fibrils of the germline variant of human λ-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stability"}],"origin":[{"dateIssuedKey":"2020","dateIssuedDisp":"October 22, 2020"}],"note":["Gesehen am 04.02.2021"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"physDesc":[{"extent":"11 S."}],"name":{"displayForm":["Tejaswini Pradhan, Karthikeyan Annamalai, Riddhiman Sarkar, Stefanie Huhn, Ute Hegenbart, Stefan Schönland, Marcus Fändrich, and Bernd Reif"]},"relHost":[{"title":[{"subtitle":"JBC","title_sort":"journal of biological chemistry","title":"The journal of biological chemistry"}],"note":["Gesehen am 19.05.2021"],"origin":[{"dateIssuedDisp":"2021-","dateIssuedKey":"2021","publisher":"Elsevier B.V. ; American Soc. of Biological Chemists ; ASBMB Publications","publisherPlace":"[Amsterdam] ; Baltimore, Md. [u.a.] ; Bethesda, Md."}],"pubHistory":["1.1905/06 -"],"type":{"media":"Online-Ressource","bibl":"periodical"},"disp":"Seeded fibrils of the germline variant of human λ-III immunoglobulin light chain FOR005 have a similar core as patient fibrils with reduced stabilityThe journal of biological chemistry","recId":"269247025","physDesc":[{"extent":"Online-Ressource"}],"name":{"displayForm":["publ. by the American Society for Biochemistry and Molecular Biology"]},"id":{"issn":["1083-351X"],"zdb":["1474604-9"],"eki":["269247025"]},"corporate":[{"display":"American Society for Biochemistry and Molecular Biology","role":"isb"}],"language":["eng"],"part":{"extent":"11","volume":"295","year":"2020","pages":"18474-18484","issue":"52","text":"295(2020), 52, Seite 18474-18484"},"titleAlt":[{"title":"JBC online"},{"title":"JBC"}]}],"recId":"1747378941","id":{"eki":["1747378941"],"doi":["10.1074/jbc.RA120.016006"]}} | ||
| SRT | |a PRADHANTEJSEEDEDFIBR2220 | ||