Knarr, Gerhard and Gething, Mary-Jane and Modrow, Susanne and Buchner, Johannes (1995) BiP Binding Sequences in Antibodies. JOURNAL OF BIOLOGICAL CHEMISTRY, 270 (46). pp. 27589-27594. ISSN 0021-9258, 1083-351X
Full text not available from this repository.Abstract
During the process of folding and assembly of antibody molecules in the endoplasmic reticulum, immunoglobulin heavy and light chains associate transiently with BiP, a resident endoplasmic reticulum protein that is a member of the Hsp70 family of molecular chaperones. Dip is thought to recognize unfolded or unassembled polypeptides by binding extended sequences of approximately seven amino acids that include bulky hydrophobic residues not normally exposed on the surface of native proteins. We used a computer algorithm developed to predict BiP binding sites within protein primary sequences to identify sites within immunoglobulin chains that might mediate their association with BiP. Very few of the sequential heptapeptides in the heavy or light chain sequences were potential Dip binding sites. Analysis of the ability of synthetic heptapeptides corresponding to 24 potential sites in heavy chains to stimulate the ATPase activity of BiP indicated that at least half of them were authentic Dip binding sequences. These sequences were not confined to a single domain of the heavy chain but were distributed within both the V-H and C-H domains. interestingly, when the BiP binding sequences were mapped onto the three dimensional structure of the Fd antibody fragment, the majority involve residues that participate in contact sites between the heavy and light chains. Therefore, we suggest that in. vivo BiP chaperones the folding and assembly of antibody molecules by binding to hydrophobic surface regions on the isolated immunoglobulin chains that subsequently participate in interchain contacts.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MOLECULAR CHAPERONE BIP; PEPTIDE-BINDING; HEAVY-CHAINS; LIGHT-CHAINS; PROTEIN; IMMUNOGLOBULIN; ASSOCIATION; SPECIFICITY; TRANSPORT; RELEASE |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Nov 2023 10:50 |
| Last Modified: | 17 Nov 2023 10:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/52202 |
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