Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10868
Title: Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitro.
Authors: Kovac, Suzana;Ferrand, Audrey;Estève, Jean-Pierre;Mason, Anne B;Baldwin, Graham S
Affiliation: Department of Surgery, University of Melbourne, Austin Health, Victoria, Australia.
Issue Date: 31-Jul-2009
Citation: The Febs Journal 2009; 276(17): 4866-74
Abstract: Transferrin is the main iron transport protein found in the circulation, and the level of transferrin saturation in the blood is an important indicator of iron status. The peptides amidated gastrin(17) (Gamide) and glycine-extended gastrin(17) (Ggly) are well known for their roles in controlling acid secretion and as growth factors in the gastrointestinal tract. Several lines of evidence, including the facts that transferrin binds gastrin, that gastrins bind ferric ions, and that the level of expression of gastrins positively correlates with transferrin saturation, suggest the possible involvement of the transferrin-gastrin interaction in iron homeostasis. In the present work, the interaction between gastrins and transferrin has been characterized by surface plasmon resonance and covalent crosslinking. First, an interaction between iron-free apo-transferrin and Gamide or Ggly was observed. The fact that no interaction was observed in the presence of the chelator EDTA suggested that the gastrin-ferric ion complex was the interacting species. Moreover, removal of ferric ions with EDTA reduced the stability of the complex between apo-transferrin and gastrins, and no interaction was observed between Gamide or Ggly and diferric transferrin. Second, some or all of glutamates at positions 8-10 of the Ggly molecule, together with the C-terminal domain, were necessary for the interaction with apo-transferrin. Third, monoferric transferrin mutants incapable of binding iron in either the N-terminal or C-terminal lobe still bound Ggly. These findings are consistent with the hypothesis that gastrin peptides bind to nonligand residues within the open cleft in each lobe of transferrin and are involved in iron loading of transferrin in vivo.
Internal ID Number: 19664057
URI: http://ahro.austin.org.au/austinjspui/handle/1/10868
DOI: 10.1111/j.1742-4658.2009.07186.x
URL: http://www.ncbi.nlm.nih.gov/pubmed/19664057
Type: Journal Article
Subjects: Cations
Cross-Linking Reagents.chemistry
Edetic Acid.chemistry
Gastrins.chemistry.genetics
Glycine.chemistry.genetics
Iron.chemistry
Iron Chelating Agents.chemistry
Mutation
Protein Binding
Transferrin.chemistry
Appears in Collections:Journal articles

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