title: A new consensus sequence for phosphatidylserine recognition by annexins.
abstract: Annexins are abundant and ubiquitous proteins that bind, by their four structurally identical domain cores, to phosphatidylserine-containing membranes in the presence of Ca2+. Using molecular simulation and mutagenesis, we have identified a new phosphatidylserine-binding site in annexin V domain 1 and established its structure. The residues involved in this site constitute a consensus sequence highly conserved in all annexins. Remarkably, this consensus sequence is exclusively found in domains 1 or 2, sometimes in both, but never in domains 3 and 4. Such a pattern actually delineates three classes of annexins, shedding new light on the role played by the four-domain core of annexins that could encode specific information discriminating the different annexins that compete within a given cell for membrane binding. Our findings thus provide new strategies for understanding the regulation of the cellular functions of annexins.
authors.affiliation: Commissariat à l'Energie Atomique-Saclay, Département de Biologie Joliot-Curie, Service de Biophysique des Fonctions Membranaires and URA CNRS 2096, Bât. 532, 91191 Gif-sur-Yvette cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Montaville
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Neumann
authors.forename: Francoise
authors.initials: F
authors.lastname: Russo-Marie
authors.forename: Francoise
authors.initials: F
authors.lastname: Ochsenbein
authors.forename: Alain
authors.initials: A
authors.lastname: Sanson
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017306:Annexin A2 / Q000737:chemistry; D017302:Annexins / Q000737:chemistry*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D016384:Consensus Sequence; D017124:Conserved Sequence; D018076:DNA, Complementary; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010718:Phosphatidylserines / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D020349:Surface Plasmon Resonance
chemical_list: D017306:Annexin A2; D017302:Annexins; D018076:DNA, Complementary; D010718:Phosphatidylserines; D011993:Recombinant Fusion Proteins; D002118:Calcium