title: Identification of the calmodulin binding domain of alpha-fodrin and implications for folding.
abstract: A cDNA clone producing a protein that binds calmodulin has been isolated from a mouse macrophage library. The cDNA was sequenced and identified as coding for fodrin. By deleting part of the sequence, the calmodulin binding domain was located. The site is situated on repeat 11 of fodrin probably on its extra arm. This part of the sequence exhibits great similarity to other calmodulin binding proteins. Analysis of the sequence and spatial structure of calmodulin revealed a domain which is quite complementary to the sequence identified on fodrin. These results provide a new insight into the structure of fodrin and consequently into the structure of proteins of the spectrin family. A model for the general folding of these molecules is proposed, involving a simple three-layer folding. The structure was further corroborated by analysis of charge distribution in the vicinity of the calmodulin binding site. The folding we propose is in good agreement with digestion experiments and explains observations in diseases resulting from mutations of human spectrin.
authors.affiliation: U-249 INSERM, Montpellier, France.
authors.forename: J
authors.initials: J
authors.lastname: Sri Widada
authors.forename: J
authors.initials: J
authors.lastname: Asselin
authors.forename: S
authors.initials: S
authors.lastname: Colote
authors.forename: C
authors.initials: C
authors.lastname: Ferraz
authors.forename: G
authors.initials: G
authors.lastname: Travé
authors.forename: M
authors.initials: M
authors.lastname: Afshar
authors.forename: J
authors.initials: J
authors.lastname: Haiech
authors.forename: J P
authors.initials: JP
authors.lastname: Liautard
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002147:Calmodulin / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D013049:Spectrin / Q000235:genetics / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D002352:Carrier Proteins; D008840:Microfilament Proteins; D013049:Spectrin