Abstract
To determine the structure of three nuclear localizing lupus anti-DNA immunoglobulins (Igs) and to search for clues to mechanisms of cellular and/or nuclear access, their H- and L-chain variable region sequences were determined and subjected to three-dimensional modeling. Although the results indicate heterogeneity in their primary structures, the H chains are encoded by 3 members of the J558 VH gene family with a common tertiary conformation that is not shared by a J558-encoded nonnuclear localizing anti-DNA control Ig. Furthermore, at least two of the Igs share a conformational motif in the H-chain CDR3, and all three Igs contain multiple positively charged amino acids in their CDRs, resembling nuclear localization signals that direct protein nuclear import. Notably, each VH and VK gene is also found recurrently among previously described autoantibodies. Molecular analysis further indicates that both germline-encoded and significantly mutated V genes can generate nuclear localizing anti-DNA Ig.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 186-206 |
| Number of pages | 21 |
| Journal | Immunologic Research |
| Volume | 13 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Jun 1 1994 |
| Externally published | Yes |
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Keywords
- Anti-DNA
- Antibody modeling
- Autoantibodies
- Lupus
- Nuclear localization
- Tertiary conformation
- V genes, variable-region genes
ASJC Scopus subject areas
- Immunology
Cite this
Molecular and structural analysis of nuclear localizing anti-DNA lupus antibodies. / Foster, Mary H.; Kieber-Emmons, Thomas; Ohliger, Michael; Madaio, Michael P.
In: Immunologic Research, Vol. 13, No. 2-3, 01.06.1994, p. 186-206.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular and structural analysis of nuclear localizing anti-DNA lupus antibodies
AU - Foster, Mary H.
AU - Kieber-Emmons, Thomas
AU - Ohliger, Michael
AU - Madaio, Michael P.
PY - 1994/6/1
Y1 - 1994/6/1
N2 - To determine the structure of three nuclear localizing lupus anti-DNA immunoglobulins (Igs) and to search for clues to mechanisms of cellular and/or nuclear access, their H- and L-chain variable region sequences were determined and subjected to three-dimensional modeling. Although the results indicate heterogeneity in their primary structures, the H chains are encoded by 3 members of the J558 VH gene family with a common tertiary conformation that is not shared by a J558-encoded nonnuclear localizing anti-DNA control Ig. Furthermore, at least two of the Igs share a conformational motif in the H-chain CDR3, and all three Igs contain multiple positively charged amino acids in their CDRs, resembling nuclear localization signals that direct protein nuclear import. Notably, each VH and VK gene is also found recurrently among previously described autoantibodies. Molecular analysis further indicates that both germline-encoded and significantly mutated V genes can generate nuclear localizing anti-DNA Ig.
AB - To determine the structure of three nuclear localizing lupus anti-DNA immunoglobulins (Igs) and to search for clues to mechanisms of cellular and/or nuclear access, their H- and L-chain variable region sequences were determined and subjected to three-dimensional modeling. Although the results indicate heterogeneity in their primary structures, the H chains are encoded by 3 members of the J558 VH gene family with a common tertiary conformation that is not shared by a J558-encoded nonnuclear localizing anti-DNA control Ig. Furthermore, at least two of the Igs share a conformational motif in the H-chain CDR3, and all three Igs contain multiple positively charged amino acids in their CDRs, resembling nuclear localization signals that direct protein nuclear import. Notably, each VH and VK gene is also found recurrently among previously described autoantibodies. Molecular analysis further indicates that both germline-encoded and significantly mutated V genes can generate nuclear localizing anti-DNA Ig.
KW - Anti-DNA
KW - Antibody modeling
KW - Autoantibodies
KW - Lupus
KW - Nuclear localization
KW - Tertiary conformation
KW - V genes, variable-region genes
UR - http://www.scopus.com/inward/record.url?scp=0028609559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028609559&partnerID=8YFLogxK
U2 - 10.1007/BF02918279
DO - 10.1007/BF02918279
M3 - Article
C2 - 7775809
AN - SCOPUS:0028609559
VL - 13
SP - 186
EP - 206
JO - Immunologic Research
JF - Immunologic Research
SN - 0257-277X
IS - 2-3
ER -