The structure and dynamics of rat apo-cellular retinol-binding protein II in solution: comparison with the X-ray structure 1 1Edited by P. E. Wright

Lü, Jianyun; Lin, Chan-Lan; Tang, Changguo; Ponder, Jay W.; Kao, Jeff; Cistola, David P.; Li, Ellen

doi:10.1006/jmbi.1999.2544

Cited by 36 publications

(44 citation statements)

References 42 publications

(53 reference statements)

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“…Contrary to an earlier report on the solution structure of rat apo CRBP-II, suggesting an increased accessibility to the retinol binding cavity due, in part, to the unwinding of helix ␣ II ( 28 ), our NMR results show that the segment F27-V34 does adopt a helical conformation, in agreement with the crystal structures of rat and human apo CRBP-II ( 29,41 ). Apparently, the experimental conditions in the previous NMR study ( 28 ) did not allow the observation of several crucial NOE connectivities, thus pointing to a disordered conformation rather than to a helical fold. Other members of the i-LBP family also featured weak signal intensities of the backbone amides belonging to helix ␣ II, as they frequently either exhibit strong line-broadening or exist as several distinct spin systems ( 21,25,51,53 ).…”

Section: Discussioncontrasting

confidence: 57%

“…Moreover, according to the chemical shift index approach ( 38 ) In order to examine whether these fi ndings are valid also at a higher, more physiological pH, the abovedescribed experiments were repeated at pH 7.4 like in the previous NMR study ( 28 ). As expected, the NOE pattern defi ning helix ␣ II was less complete due to stronger linebroadening effects that affected mainly the weak long-distance NOE signals ( Fig.…”

Section: Structural Comparison Between Apo and Holo Crbp-iimentioning

confidence: 80%

“…We were able to identify the characteristic NOE connectivities that defi ne helix ␣ II by collecting NMR data at different pH values and taking advantage of the higher spectral resolution of homonuclear 2D-NOESY spectra, which were analyzed in combination with 15 N-edited 3D-NOESY data. Hence, the previously suggested structural implications for the mechanism of retinol binding to CRBP II ( 28 ), including a ligand-induced coil-tohelix transition ( 30 ), need to be reconsidered.…”

Section: Discussionmentioning

confidence: 99%

“…In the case of CRBP-I in solution, the topology of the entry portal is essentially identical in the presence and absence of retinol ( 25 ). Similarly, apo and holo CRBP-II in the crystal exhibit only small differences in the backbone fold ( 29 ), with a very low total C ␣ trace root mean square deviation (0.23 Å), while in solution the helix ␣ II segment of the typical helix-turn-helix motif has been described as unwound in the apo form ( 28 ). The reported discrepancy between the solution and crystal structures of apo CRBP-II (see Fig.…”

Section: Structural Comparison Between Apo and Holo Crbp-iimentioning

confidence: 92%

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New insights on the protein-ligand interaction differences between the two primary cellular retinol carriers

Franzoni

Cavazzini

Rossi

et al. 2010

Journal of Lipid Research

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Section: Discussioncontrasting

confidence: 57%

Section: Structural Comparison Between Apo and Holo Crbp-iimentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Structural Comparison Between Apo and Holo Crbp-iimentioning

confidence: 92%

See 2 more Smart Citations

New insights on the protein-ligand interaction differences between the two primary cellular retinol carriers

Franzoni

Cavazzini

Rossi

et al. 2010

Journal of Lipid Research

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“…The helical region is additionally thought to be a key determinant in the interactions of iLBPs with membranes [32,33]. An important difference though is that, while in FABPs [26] and some of the reported CRBP structures [34,35] the helical region shows a considerable disorder in the apo state, in human I-BABP it is well defined in both the free [9] and the bound forms.…”

Section: Ligand Induced Conformational Changes Versus Millisecond Motmentioning

confidence: 98%

Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and glycochenodeoxycholate obtained from solution NMR

et al. 2016

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Besides aiding digestion, bile salts are important signal molecules exhibiting a regulatory role in metabolic processes. Human ileal bile acid binding protein (I‐BABP) is an intracellular carrier of bile salts in the epithelial cells of the distal small intestine and has a key role in the enterohepatic circulation of bile salts. Positive binding cooperativity combined with site selectivity of glycocholate and glycochenodeoxycholate, the two most abundant bile salts in the human body, make human I‐BABP a unique member of the family of intracellular lipid binding proteins. Solution NMR structure of the ternary complex of human I‐BABP with glycocholate and glycochenodeoxycholate reveals an extensive network of hydrogen bonds and hydrophobic interactions stabilizing the bound bile salts. Conformational changes accompanying bile salt binding affects four major regions in the protein including the C/D, E/F and G/H loops as well as the helical segment. Most of these protein regions coincide with a previously described network of millisecond time scale fluctuations in the apo protein, a motion absent in the bound state. Comparison of the heterotypic doubly ligated complex with the unligated form provides further evidence of a conformation selection mechanism of ligand entry. Structural and dynamic aspects of human I‐BABP–bile salt interaction are discussed and compared with characteristics of ligand binding in other members of the intracellular lipid binding protein family. Protein Data Bank Accession Numbers The coordinates of the 10 lowest energy structures of the human I‐BABP : GCDA : GCA complex as well as the distance restraints used to calculate the final ensemble have been deposited in the Brookhaven Protein Data Bank with accession number http://www.rcsb.org/pdb/search/structidSearch.do?structureId=2MM3.

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Insights into the bile acid transportation system: The human ileal lipid‐binding protein‐cholyltaurine complex and its comparison with homologous structures

Kurz¹,

Brachvogel²,

Matter³

et al. 2002

Proteins

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Bile acids are generated in vivo from cholesterol in the liver, and they undergo an enterohepatic circulation involving the small intestine, liver, and kidney. To understand the molecular mechanism of this transportation, it is essential to gain insight into the three-dimensional (3D) structures of proteins involved in the bile acid recycling in free and complexed form and to compare them with homologous members of this protein family. Here we report the solution structure of the human ileal lipid-binding protein (ILBP) in free form and in complex with cholyltaurine. Both structures are compared with a previously published structure of the porcine ILBP-cholylglycine complex and with related lipid-binding proteins. Protein structures were determined in solution by using two-dimensional (2D)- and 3D-homo and heteronuclear NMR techniques, leading to an almost complete resonance assignment and a significant number of distance constraints for distance geometry and restrained molecular dynamics simulations. The identification of several intermolecular distance constraints unambiguously determines the cholyltaurine-binding site. The bile acid is deeply buried within ILBP with its flexible side-chain situated close to the fatty acid portal as entry region into the inner ILBP core. This binding mode differs significantly from the orientation of cholylglycine in porcine ILBP. A detailed analysis using the GRID/CPCA strategy reveals differences in favorable interactions between protein-binding sites and potential ligands. This characterization will allow for the rational design of potential inhibitors for this relevant system.

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The structure and dynamics of rat apo-cellular retinol-binding protein II in solution: comparison with the X-ray structure 1 1Edited by P. E. Wright

Cited by 36 publications

References 42 publications

New insights on the protein-ligand interaction differences between the two primary cellular retinol carriers

New insights on the protein-ligand interaction differences between the two primary cellular retinol carriers

Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and glycochenodeoxycholate obtained from solution NMR

Insights into the bile acid transportation system: The human ileal lipid‐binding protein‐cholyltaurine complex and its comparison with homologous structures

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