title: Exploring the folding pathways of annexin I, a multidomain protein. I. non-native structures stabilize the partially folded state of the isolated domain 2 of annexin I.
abstract: Proteins of the annexin family constitute very attractive models because of their four approximately 70 residue domains, D1 to D4, exhibiting an identical topology comprising five helix segments with only a limited sequence homology of approximately 30%. We focus on the isolated D2 domain, which is only partially folded. A detailed analysis of this equilibrium partially folded state in aqueous solution and micellar solution using 15N-1H multidimensional NMR is presented. Comparison of the residual structure of the entire domain with that of shorter fragments indicates the presence of long-range transient hydrophobic interactions that slightly stabilize the secondary structure elements. The unfolded domain tends to behave as a four-helix, rather than as a five-helix domain. The ensemble of residual structures comprises: (i) a set of native structures consisting of three regions with large helix populations, in rather sharp correspondence with A, B and E helices, and a small helix population in the second part of the C helix; (ii) a set of non-native local structures corresponding to turn-like structures stabilized by several side-chain to side-chain interactions and helix-disruptive side-chains to backbone interactions. Remarkably, residues involved in these local non-native interactions are also involved, in the native structure, in structurally important non-local interactions. During the folding process of annexin I, the local non-native interactions have to switch to native long-range interactions. This structural switch reveals the existence of a sequence-encoded regulation of the folding pathways and kinetics, and emphasizes the key role of the non-native local structures in this regulation.
authors.affiliation: Département de Biologie Cellulaire et Moléculaire Section de Biophysique des Protéines et des Membranes and URA CNRS, 2096, Gif sur Yvette Cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Cordier-Ochsenbein
authors.forename: R
authors.initials: R
authors.lastname: Guerois
authors.forename: F
authors.initials: F
authors.lastname: Baleux
authors.forename: T
authors.initials: T
authors.lastname: Huynh-Dinh
authors.forename: P N
authors.initials: PN
authors.lastname: Lirsac
authors.forename: F
authors.initials: F
authors.lastname: Russo-Marie
authors.forename: J M
authors.initials: JM
authors.lastname: Neumann
authors.forename: A
authors.initials: A
authors.lastname: Sanson
mesh_terms: D017305:Annexin A1 / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010446:Peptide Fragments / Q000737:chemistry*; D011138:Polytetrafluoroethylene / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D017510:Protein Folding
chemical_list: D017305:Annexin A1; D008823:Micelles; D010446:Peptide Fragments; D011138:Polytetrafluoroethylene