title: Annexins possess functionally distinguishable Ca2+ and phospholipid binding domains.
abstract: All annexins bind Ca2+ and phospholipids, although individual annexins differ markedly in their affinities for these ligands. Annexin I binds phosphatidylserine (PS) at lower [Ca2+] than annexin V, while annexin V exhibits a higher affinity for PS than does annexin I. To identify the structural determinants of these properties, we characterized a series of chimeric annexins. A chimera containing repeat 1 of annexin V used to repeats 2, 3, and 4 of annexin I exhibited a Ca2+ requirement for PS binding close to that of annexin I, while chimeras containing repeat 1 of annexin I fused to repeats 2, 3, and 4 of annexin V required higher [Ca2+], similar to that of annexin V. In contrast, the overall affinity for PS vesicles was determined by the source of repeat 1. The chimera that contained repeat 1 of annexin V exhibited a high affinity for PS, while a chimera that contained repeat 1 of annexin I had a low affinity for PS similar to that of annexin I. We conclude that the [Ca2+] requirement for phospholipid binding and the overall phospholipid affinity of annexins are determined by distinct domains.
authors.affiliation: Department of Medicine, University of California, San Francisco 94143-0868.
authors.forename: J D
authors.initials: JD
authors.lastname: Ernst
authors.forename: A
authors.initials: A
authors.lastname: Mall
authors.forename: G
authors.initials: G
authors.lastname: Chew
mesh_terms: D017302:Annexins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010718:Phosphatidylserines / Q000378:metabolism*; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D017302:Annexins; D017931:DNA Primers; D010718:Phosphatidylserines; D011993:Recombinant Fusion Proteins; D002118:Calcium