Structural Requirements for Cooperativity in Ileal Bile Acid-binding Proteins

被引:16
作者
Zanzoni, Serena [1 ]
Assfalg, Michael [1 ]
Giorgetti, Alejandro [1 ,2 ,3 ]
D'Onofrio, Mariapina [1 ]
Molinari, Henriette [1 ]
机构
[1] Univ Verona, Dept Biotechnol, I-37134 Verona, Italy
[2] FZ Julich, German Res Sch Simulat Sci, D-52428 Julich, Germany
[3] Rhein Westfal TH Aachen, D-52428 Julich, Germany
关键词
LIGAND-BINDING; SITE SELECTIVITY; NMR; DETERMINANTS; CRYSTALLOGRAPHY; IDENTIFICATION; ACTIVATION; EVOLUTION; ALLOSTERY; DYNAMICS;
D O I
10.1074/jbc.M111.261099
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ileal bile acid-binding proteins (I-BABP), belonging to the family of intracellular lipid-binding proteins, control bile acid trafficking in enterocytes and participate in regulating the homeostasis of these cholesterol-derived metabolites. I-BABP orthologues share the same structural fold and are able to host up to two ligands in their large internal cavities. However variations in the primary sequences determine differences in binding properties such as the degree of binding cooperativity. To investigate the molecular requirements for cooperativity we adopted a gain-of-function approach, exploring the possibility to turn the noncooperative chicken I-BABP (cI-BABP) into a cooperative mutant protein. To this aim we first solved the solution structure of cI-BABP in complex with two molecules of the physiological ligand glycochenodeoxycholate. A comparative structural analysis with closely related members of the same protein family provided the basis to design a double mutant (H99Q/A101S cI-BABP) capable of establishing a cooperative binding mechanism. Molecular dynamics simulation studies of the wild type and mutant complexes and essential dynamics analysis of the trajectories supported the role of the identified amino acid residues as hot spot mediators of communication between binding sites. The emerging picture is consistent with a binding mechanism that can be described as an extended conformational selection model.
引用
收藏
页码:39307 / 39317
页数:11
相关论文
共 58 条
  • [1] Argmann Carmen A, 2006, Curr Protoc Mol Biol, VChapter 29, DOI 10.1002/0471142727.mb29a03s75
  • [2] Continuous nucleocytoplasmic shuttling underlies transcriptional activation of PPARγ by FABP4
    Ayers, Stephen D.
    Nedrow, Katherine L.
    Gillilan, Richard E.
    Noy, Noa
    [J]. BIOCHEMISTRY, 2007, 46 (23) : 6744 - 6752
  • [3] Evaluating protein structures determined by structural genomics consortia
    Bhattacharya, Aneerban
    Tejero, Roberto
    Montelione, Gaetano T.
    [J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2007, 66 (04) : 778 - 795
  • [4] Crystallography & NMR system:: A new software suite for macromolecular structure determination
    Brunger, AT
    Adams, PD
    Clore, GM
    DeLano, WL
    Gros, P
    Grosse-Kunstleve, RW
    Jiang, JS
    Kuszewski, J
    Nilges, M
    Pannu, NS
    Read, RJ
    Rice, LM
    Simonson, T
    Warren, GL
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 : 905 - 921
  • [5] The X-Ray Structure of Zebrafish (Danio rerio) Ileal Bile Acid-Binding Protein Reveals the Presence of Binding Sites on the Surface of the Protein Molecule
    Capaldi, Stefano
    Saccomani, Gianmaria
    Fessas, Dimitrios
    Signorelli, Marco
    Perduca, Massimiliano
    Monaco, Hugo L.
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2009, 385 (01) : 99 - 116
  • [6] Stochastic quasi-Newton method: Application to minimal model for proteins
    Chau, C. D.
    Sevink, G. J. A.
    Fraaije, J. G. E. M.
    [J]. PHYSICAL REVIEW E, 2011, 83 (01):
  • [7] Site-Specific Investigation of the Steady-State Kinetics and Dynamics of the Multistep Binding of Bile Acid Molecules to a Lipid Carrier Protein
    Cogliati, Clelia
    Ragona, Laura
    D'Onofrio, Mariapina
    Guenther, Ulrich
    Whittaker, Sara
    Ludwig, Christian
    Tomaselli, Simona
    Assfalg, Michael
    Molinari, Henriette
    [J]. CHEMISTRY-A EUROPEAN JOURNAL, 2010, 16 (37) : 11300 - 11310
  • [8] Induced fit, conformational selection and independent dynamic segments: an extended view of binding events
    Csermely, Peter
    Palotai, Robin
    Nussinov, Ruth
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 2010, 35 (10) : 539 - 546
  • [9] Allostery and cooperativity revisited
    Cui, Qiang
    Karplus, Martin
    [J]. PROTEIN SCIENCE, 2008, 17 (08) : 1295 - 1307
  • [10] MOLECULAR MODELING - AN EXPERIMENTAL TOOL
    DARDEN, TA
    PEDERSEN, LG
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 1993, 101 (05) : 410 - 412