The University of Southampton
University of Southampton Institutional Repository

Goodpasture syndrome. Localization of the epitope for the autoantibodies to the carboxyl-terminal region of the alpha 3(IV) chain of basement membrane collagen.

Goodpasture syndrome. Localization of the epitope for the autoantibodies to the carboxyl-terminal region of the alpha 3(IV) chain of basement membrane collagen.
Goodpasture syndrome. Localization of the epitope for the autoantibodies to the carboxyl-terminal region of the alpha 3(IV) chain of basement membrane collagen.
The autoantibodies of patients with Goodpasture syndrome are primarily targeted to the noncollagenous (NC1) domain of the alpha 3(IV) chain of basement membrane collagen (Saus, J., Wieslander, J., Langeveld, J. P. M., Quinones, S., and Hudson, B. G. (1988) J. Biol. Chem. 263, 13374-13380). In the present study, the location of the Goodpasture epitope in human alpha 3NC1 was determined, and its structure was partially characterized. This was achieved by identification of regions of alpha 3NC1 which are candidates for the epitope and which are structurally unique among the five known homologous NC1 domains (alpha 1-alpha 5); amino acids that are critical for Goodpasture antibody binding, by selective chemical modifications; and regions that are critical for Goodpasture antibody binding, by synthesis of 12 alpha 3NC1 peptides and measurement of their antibody binding capacity. The carboxyl-terminal region, residues 198-233, was identified as the most likely region for the epitope. By experiment, lysine and cysteine were identified as critical amino acids for antibody binding. Three synthetic peptides were found to inhibit Goodpasture antibody binding to alpha 3NC1 markedly: a 36-mer (residues 198-233), a 12-mer (residues 222-233), and a 5-mer (residues 229-233). Together, these results strongly indicate that the Goodpasture epitope is localized to the carboxyl-terminal region of alpha 3NC1, encompassing residues 198-233 as the primary antibody interaction site and that its structure is discontinuous. These findings provide a conceptual framework for future studies to elucidate a more complete epitope structure by sequential replacement of residues encompassing the epitope using cDNA expression products and peptides synthesized chemically.
24018-24024
Kalluri, R.
bb435496-bd7e-4541-ab19-52eedc0a3a5a
Gunwar, S.
12d14d1a-c221-4f83-b13d-12fdb358c242
Reeders, S.T.
68cbd8f9-d203-4375-92dc-2ac0ca36799e
Morrison, K.E.
f00890f0-2fde-4dbd-a73b-7422e1b0ede8
Mariyama, M.
6dd0b7f2-d974-4b35-9cce-a24d5d7397b4
Ebner, K.E.
77e6016d-b6de-47f2-bb2c-3ece47188ad1
Noelken, M.E.
dccd116c-0c57-4c87-91df-465179f13a64
Hudson, B.G.
8e23e723-6310-4f09-a98c-a12724bb9576
Kalluri, R.
bb435496-bd7e-4541-ab19-52eedc0a3a5a
Gunwar, S.
12d14d1a-c221-4f83-b13d-12fdb358c242
Reeders, S.T.
68cbd8f9-d203-4375-92dc-2ac0ca36799e
Morrison, K.E.
f00890f0-2fde-4dbd-a73b-7422e1b0ede8
Mariyama, M.
6dd0b7f2-d974-4b35-9cce-a24d5d7397b4
Ebner, K.E.
77e6016d-b6de-47f2-bb2c-3ece47188ad1
Noelken, M.E.
dccd116c-0c57-4c87-91df-465179f13a64
Hudson, B.G.
8e23e723-6310-4f09-a98c-a12724bb9576

Kalluri, R., Gunwar, S., Reeders, S.T., Morrison, K.E., Mariyama, M., Ebner, K.E., Noelken, M.E. and Hudson, B.G. (1991) Goodpasture syndrome. Localization of the epitope for the autoantibodies to the carboxyl-terminal region of the alpha 3(IV) chain of basement membrane collagen. The Journal of Biological Chemistry, 266 (35), 24018-24024. (PMID:1721062)

Record type: Article

Abstract

The autoantibodies of patients with Goodpasture syndrome are primarily targeted to the noncollagenous (NC1) domain of the alpha 3(IV) chain of basement membrane collagen (Saus, J., Wieslander, J., Langeveld, J. P. M., Quinones, S., and Hudson, B. G. (1988) J. Biol. Chem. 263, 13374-13380). In the present study, the location of the Goodpasture epitope in human alpha 3NC1 was determined, and its structure was partially characterized. This was achieved by identification of regions of alpha 3NC1 which are candidates for the epitope and which are structurally unique among the five known homologous NC1 domains (alpha 1-alpha 5); amino acids that are critical for Goodpasture antibody binding, by selective chemical modifications; and regions that are critical for Goodpasture antibody binding, by synthesis of 12 alpha 3NC1 peptides and measurement of their antibody binding capacity. The carboxyl-terminal region, residues 198-233, was identified as the most likely region for the epitope. By experiment, lysine and cysteine were identified as critical amino acids for antibody binding. Three synthetic peptides were found to inhibit Goodpasture antibody binding to alpha 3NC1 markedly: a 36-mer (residues 198-233), a 12-mer (residues 222-233), and a 5-mer (residues 229-233). Together, these results strongly indicate that the Goodpasture epitope is localized to the carboxyl-terminal region of alpha 3NC1, encompassing residues 198-233 as the primary antibody interaction site and that its structure is discontinuous. These findings provide a conceptual framework for future studies to elucidate a more complete epitope structure by sequential replacement of residues encompassing the epitope using cDNA expression products and peptides synthesized chemically.

Full text not available from this repository.

More information

Published date: 15 December 1991
Organisations: Medical Education

Identifiers

Local EPrints ID: 399572
URI: http://eprints.soton.ac.uk/id/eprint/399572
PURE UUID: 63377897-70ff-45f1-bef9-f3d8d07e22a9
ORCID for K.E. Morrison: ORCID iD orcid.org/0000-0003-0216-5717

Catalogue record

Date deposited: 18 Aug 2016 13:51
Last modified: 06 Jun 2018 12:19

Export record

Contributors

Author: R. Kalluri
Author: S. Gunwar
Author: S.T. Reeders
Author: K.E. Morrison ORCID iD
Author: M. Mariyama
Author: K.E. Ebner
Author: M.E. Noelken
Author: B.G. Hudson

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×