2LBA

Solution structure of chicken ileal BABP in complex with glycochenodeoxycholic acid

2LBA の概要

• エントリーDOI: 10.2210/pdb2lba/pdb
• NMR情報: BMRB: 17551
• 分子名称: BABP protein, GLYCOCHENODEOXYCHOLIC ACID (2 entities in total)
• 機能のキーワード: ileal bile acid binding protein, lipid binding protein
• 由来する生物種: Gallus gallus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16074.47

構造登録者

Zanzoni, S.,Assfalg, M.,Giorgetti, A.,D'Onofrio, M.,Molinari, H. (登録日: 2011-03-28, 公開日: 2011-09-14, 最終更新日: 2024-05-15)

主引用文献

Zanzoni, S.,Assfalg, M.,Giorgetti, A.,D'Onofrio, M.,Molinari, H.
Structural Requirements for Cooperativity in Ileal Bile Acid-binding Proteins.
J.Biol.Chem., 286:39307-39317, 2011

PubMed Abstract: 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.

PubMed: 21917914
DOI: 10.1074/jbc.M111.261099

実験手法

SOLUTION NMR