Reverse-engineering the anti-MUC1 antibody 139H2 by mass spectrometry-based de novo sequencing
© 2024 Peng et al..
Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at mucosal surfaces. MUC1 has a barrier function against bacterial invasion and is well known for its aberrant expression and glycosylation in adenocarcinomas. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily O-linked glycosylated. Monoclonal antibodies against the MUC1 VNTR are powerful research tools with applications in the diagnosis and treatment of MUC1-expressing cancers. Here, we report direct mass spectrometry-based sequencing of anti-MUC1 hybridoma-derived 139H2 IgG, enabling reverse-engineering of the functional recombinant monoclonal antibody. The crystal structure of the 139H2 Fab fragment in complex with the MUC1 epitope was solved, revealing the molecular basis of 139H2 binding specificity to MUC1 and its tolerance to O-glycosylation of the VNTR. The available sequence of 139H2 will allow further development of MUC1-related diagnostic, targeting, and treatment strategies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
|---|---|
| Enthalten in: |
Life science alliance - 7(2024), 6 vom: 09. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Peng, Weiwei [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibodies, Monoclonal |
|---|
| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 23.03.2024 published: Electronic-Print PDB: 8P6I Citation Status MEDLINE |
|---|
| doi: |
10.26508/lsa.202302366 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369983033 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369983033 | ||
| 003 | DE-627 | ||
| 005 | 20240323235521.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240322s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.26508/lsa.202302366 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1342.xml |
| 035 | |a (DE-627)NLM369983033 | ||
| 035 | |a (NLM)38508723 | ||
| 035 | |a (PII)e202302366 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Peng, Weiwei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Reverse-engineering the anti-MUC1 antibody 139H2 by mass spectrometry-based de novo sequencing |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.03.2024 | ||
| 500 | |a Date Revised 23.03.2024 | ||
| 500 | |a published: Electronic-Print | ||
| 500 | |a PDB: 8P6I | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 Peng et al. | ||
| 520 | |a Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at mucosal surfaces. MUC1 has a barrier function against bacterial invasion and is well known for its aberrant expression and glycosylation in adenocarcinomas. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily O-linked glycosylated. Monoclonal antibodies against the MUC1 VNTR are powerful research tools with applications in the diagnosis and treatment of MUC1-expressing cancers. Here, we report direct mass spectrometry-based sequencing of anti-MUC1 hybridoma-derived 139H2 IgG, enabling reverse-engineering of the functional recombinant monoclonal antibody. The crystal structure of the 139H2 Fab fragment in complex with the MUC1 epitope was solved, revealing the molecular basis of 139H2 binding specificity to MUC1 and its tolerance to O-glycosylation of the VNTR. The available sequence of 139H2 will allow further development of MUC1-related diagnostic, targeting, and treatment strategies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Mucin-1 |2 NLM | |
| 650 | 7 | |a Mucins |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a MUC1 protein, human |2 NLM | |
| 700 | 1 | |a Giesbers, Koen Cap |e verfasserin |4 aut | |
| 700 | 1 | |a Šiborová, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Beugelink, J Wouter |e verfasserin |4 aut | |
| 700 | 1 | |a Pronker, Matti F |e verfasserin |4 aut | |
| 700 | 1 | |a Schulte, Douwe |e verfasserin |4 aut | |
| 700 | 1 | |a Hilkens, John |e verfasserin |4 aut | |
| 700 | 1 | |a Janssen, Bert Jc |e verfasserin |4 aut | |
| 700 | 1 | |a Strijbis, Karin |e verfasserin |4 aut | |
| 700 | 1 | |a Snijder, Joost |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Life science alliance |d 2018 |g 7(2024), 6 vom: 09. März |w (DE-627)NLM286067536 |x 2575-1077 |7 nnns |
| 773 | 1 | 8 | |g volume:7 |g year:2024 |g number:6 |g day:09 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.26508/lsa.202302366 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 7 |j 2024 |e 6 |b 09 |c 03 | ||