Publications

Structural requirements for cooperativity in ileal bile acid-binding proteins.  (2011)

Authors:
Zanzoni S.; Assfalg M.; Giorgetti A.; D'Onofrio M.; Molinari H.
Title:
Structural requirements for cooperativity in ileal bile acid-binding proteins.
Year:
2011
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Language:
Inglese
Format:
A Stampa
Referee:
Name of journal:
JBC
ISSN of journal:
0021-9258
N° Volume:
286
Number or Folder:
45
Page numbers:
39307-39317
Keyword:
cooperativity; bile acid binding proteins; structure
Short description of contents:
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.
Product ID:
63776
Handle IRIS:
11562/373414
Deposited On:
November 16, 2011
Last Modified:
January 31, 2019
Bibliographic citation:
Zanzoni S.; Assfalg M.; Giorgetti A.; D'Onofrio M.; Molinari H., Structural requirements for cooperativity in ileal bile acid-binding proteins. «JBC» , vol. 286 , n. 452011pp. 39307-39317

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo IRIS

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Dalla comprensione dell’attivazione allosterica di fatty acid binding proteins modulata dall'interazione con membrane cellulari e leganti, al disegno di nuovi inibitori della cattura di lipidi Department Biotecnologie Michael Assfalg
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