title: Annexin I and annexin II N-terminal peptides binding to S100 protein family members: specificity and thermodynamic characterization.
abstract: The S100 proteins make up a family of dimeric calcium binding proteins that function in response to changing calcium levels. Several S100 binding proteins have been identified; however, the exact biological functions of the S100 proteins are largely unknown as there are several factors which modulate their functions. To address these issues, the specificity of binding of representative members of the human S100 proteins to short N-terminal peptides of annexin I (AnI) and annexin II (AnII) was investigated under controlled experimental conditions. AnI and AnII have been shown previously to interact with S100A11 and S100A10, respectively. This provided a unique opportunity to determine their binding specificity with the other members of the human S100 protein family. It was found that AnI binds S100A6 or S100A11 while AnII binds S100A10 or S100A11. This is the first report of the interaction between S100A6 and AnI. The fact that AnI and AnII bind to selected members of the S100 protein family shows that these interactions are specific and that the mode of binding is different from that of calmodulin, as it was found not to bind AnI or AnII. From the analysis of the thermodynamics of interactions, the binding seems to be entropically driven. It was found that both AnI and AnII undergo a coil-to-helix transition upon binding to their respective binding partners. The observation that there is an overlap in functionality is not surprising due to considerable sequence homology between S100 protein family members. In fact, the functional overlap can explain previous failures of S100 knockout constructs to show any detectable changes in phenotype despite numerous implications of these proteins in important cellular processes.
authors.affiliation: Department of Biology, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Werner W
authors.initials: WW
authors.lastname: Streicher
authors.forename: Maria M
authors.initials: MM
authors.lastname: Lopez
authors.forename: George I
authors.initials: GI
authors.lastname: Makhatadze
mesh_terms: D000595:Amino Acid Sequence; D017305:Annexin A1 / Q000737:chemistry* / Q000378:metabolism; D017306:Annexin A2 / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D009418:S100 Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D017305:Annexin A1; D017306:Annexin A2; D010455:Peptides; D009418:S100 Proteins