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Structural studies on rhodopsins

Structural studies on rhodopsins
Structural studies on rhodopsins

In this work, camel rhodopsin was prepared for the first time and its molecular weight was estimated by sodium dodecylsulphate polyacrylamide gel electrophoresis and amino acid analysis. It was found that the molecular weight of the camel rhodopsin (approx. 41200) was higher than that of bovine rhodopsin (39800). Structural studies on rhodopsins from bovine, camel and rat were also carried out in this work by raising polyclonal antibodies against bovine rhodopsin as well as against the three fragments (heavy, medium and light) produced by treating bovine rhodopsin with papain. These studies showed that the three rhodopsins (bovine, rat and camel) share common antigenic domains. The main emphasis in the thesis however was to identify the cysteine residues involved in the formation of the disulphide bonds in bovine rhodopsin. In these studies, iodo[2-14C] acetic acid was used to modify 5.8-6 cysteine residues under non-reducing conditions. After reduction of the disulphide bonds with an excess of β-mercaptoethanol followed by dialysis under extreme anaerobic conditions, iodo [2-^3H] acetic acid was used to covalently modify another 3.4-4 cysteine residues. Peptide purification and sequencing has unambiguously shown that cysteine residues at positions 316 and 167 of the rhodopsin polypeptide chain were modified with ^14C only and therefore present in rhodopsin in the thiol form. On the other hand, cysteine residues at positions 322 and 323 were modified with ^3H and therefore are suggested to participate in the formation of one of the two disulphide bonds. The second disulphide bond in bovine rhodopsin was identified by indirect methods. In these experiments, when the mixture of water-soluble peptides obtained from the CNBr cleavage of the doubly labelled protein was subjected to Edman degradation, cycle four released a significant amount of ^3H and ^14C which by h.p.l.c. analysis was found to be associated with carboxymethylcysteine. The ^14C released in this cycle must have come from cysteine 167 whereas the ^3H was suggested to come from cysteine 187. Therefore cysteine 187 may be involved in the formation of the second disulphide bond in bovine rhodopsin. The earlier studies of Davison and Findlay (1986) had led to the suggestion that cysteine 110 may form a disulphide bond with another residue. Combining our result with those of Davison and Findlay allows the deduction that the second disulphide bond of rhodopsin may be between cysteine 110 and cysteine 187. This suggestion is in good agreement with the prediction made from a structural model of ovine rhodopsin proposed by Findlay and Pappin (1986). (D82737)

University of Southampton
Al-Saleh, Saad Saleh Mohammed
Al-Saleh, Saad Saleh Mohammed

Al-Saleh, Saad Saleh Mohammed (1987) Structural studies on rhodopsins. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

In this work, camel rhodopsin was prepared for the first time and its molecular weight was estimated by sodium dodecylsulphate polyacrylamide gel electrophoresis and amino acid analysis. It was found that the molecular weight of the camel rhodopsin (approx. 41200) was higher than that of bovine rhodopsin (39800). Structural studies on rhodopsins from bovine, camel and rat were also carried out in this work by raising polyclonal antibodies against bovine rhodopsin as well as against the three fragments (heavy, medium and light) produced by treating bovine rhodopsin with papain. These studies showed that the three rhodopsins (bovine, rat and camel) share common antigenic domains. The main emphasis in the thesis however was to identify the cysteine residues involved in the formation of the disulphide bonds in bovine rhodopsin. In these studies, iodo[2-14C] acetic acid was used to modify 5.8-6 cysteine residues under non-reducing conditions. After reduction of the disulphide bonds with an excess of β-mercaptoethanol followed by dialysis under extreme anaerobic conditions, iodo [2-^3H] acetic acid was used to covalently modify another 3.4-4 cysteine residues. Peptide purification and sequencing has unambiguously shown that cysteine residues at positions 316 and 167 of the rhodopsin polypeptide chain were modified with ^14C only and therefore present in rhodopsin in the thiol form. On the other hand, cysteine residues at positions 322 and 323 were modified with ^3H and therefore are suggested to participate in the formation of one of the two disulphide bonds. The second disulphide bond in bovine rhodopsin was identified by indirect methods. In these experiments, when the mixture of water-soluble peptides obtained from the CNBr cleavage of the doubly labelled protein was subjected to Edman degradation, cycle four released a significant amount of ^3H and ^14C which by h.p.l.c. analysis was found to be associated with carboxymethylcysteine. The ^14C released in this cycle must have come from cysteine 167 whereas the ^3H was suggested to come from cysteine 187. Therefore cysteine 187 may be involved in the formation of the second disulphide bond in bovine rhodopsin. The earlier studies of Davison and Findlay (1986) had led to the suggestion that cysteine 110 may form a disulphide bond with another residue. Combining our result with those of Davison and Findlay allows the deduction that the second disulphide bond of rhodopsin may be between cysteine 110 and cysteine 187. This suggestion is in good agreement with the prediction made from a structural model of ovine rhodopsin proposed by Findlay and Pappin (1986). (D82737)

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Published date: 1987

Identifiers

Local EPrints ID: 461919
URI: http://eprints.soton.ac.uk/id/eprint/461919
PURE UUID: 48ee277f-5f30-4b97-a33e-12eb023ce66b

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Date deposited: 04 Jul 2022 18:58
Last modified: 04 Jul 2022 18:58

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Author: Saad Saleh Mohammed Al-Saleh

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