CRABP I ( Cellular Retinoic Acid Binding Protein )

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Bold textOne of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.

Cellular retinoic acid binding protein I (CRABP I) (PDB code 1cbs)

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Molecular Playground banner: CRABP I, a model protein to understand protein folding.

Molecular Playground banner: CRABP I, a carrier protein for retinoic acid, has an important role for vision.

Cellular Retinoic Acid Binding Proteins(CRABPs) are small intracellular proteins (15.5 kDa) that belong to the family of intracellular lipid binding proteins (iLBP) which bind small hydrophobic ligands. There are two types of CRABPs, CRABP I and CRABP II. They seem to play a role in controlling Retinoic Acid(RA)-mediated differentiation and proliferation processes [1]. During embryonic development, the spatial and temporal expression of the CRABP gene appears to be strictly regulated [2]. Therefore, it has been suggested that CRABP could be involved in the formation of gradients of RA across various developing tissues. Although the structure of CRABP I is similar to the cellular retinol-binding proteins, it binds only retinoic acid at specific sites within the nucleus, which may contribute to vitamin A-directed differentiation in epithelial tissue.



Proteins in iLBP family have very high structural conservation despite having very low sequence identities [3]. Similar to other members of the iLBP family, (PDBID: 1CBI) has two orthogonal five-stranded with a between the first and the second β-strands,showing α+β secondary domains. It contains a very large solvent accessible central cavity that binds (PDBID: 1CBS). This conserved is contained between strand 4 and 5 and has no inter-strand hydrogen bonds but is compensated by the presence of ordered water molecules. The helix-turn-helix motif between the first and second strands acts as a on the ligand binding pocket. Strands 7 and 8 are connected by the which has variable lengths within the family. There are 15 fully residues in CRABP I, seven are found in the helix I and II and 5 are in the β-barrel closure [4].

The RA/CRABP interaction is predominantly hydrophobic, as the ligand forms ten contacts with non-polar side chains and only one salt bridge. The β-barrel contains a poorly accessible hydrophobic ligand-binding cavity. For Chain A, the residues in of CRABP I to RA correspond to PRO39,THR56, LEU120, ARG131, and TYR133. In case of Chain B, even though MET 27 is not one of the residues in chain B, it can be one of the the to RA which is bound to PRO39, THR56, LEU120, ARG131, and TYR133 in chain B of CRABP I. Comparison of the and the structure of the proteins in the iLBP family does not reveal a significant opening large enough to allow ligand entry and release [5]. Entry of RA into the cavity of CRABPs is proposed to occur via a region of the protein comprising determinants from the βC-D loop, the βE-F loop and the N-terminal region of helix II. This region of the protein referred to as the “portal” region of the protein has been extensively studied in other members of the iLBP family, in particular in the fatty acid binding protein, by X-ray crystallography, mutational analysis and multidimensional NMR [6].

See Also

3D structure of Cellular retinoic acid-binding protein


2cbr - hCRABP I – human
1cbr - CRABP I + retinoic acid – mouse


2fs6, 2fs7 - hCRABP II
1blr - hCRABP II – NMR
3fek, 3fel, 3fen, 3fa7, 3fa8, 3fa9, 3i17, 3d95, 3d96, 3d97, 2frs - hCRABP II (mutant)
3f8a, 3f9d, 3fa6, 3cr6, 2g79, 2g7b – hCRABP II (mutant) + retinal analog
3cwk, 2g78 – hCRABP II (mutant) + retinoic acid
2fr3, 2cbs, 3cbs, 1cbq, 1cbs – hCRABP II + retinoic acid
3fep - hCRABP II (mutant) + ligand


  • [1] Venepally, P. et al. Biochemistry. 35, 9974-9982 (1996) PMID: 8756459 [PubMed - indexed for MEDLINE]
  • [2] Vaessen, et al. Differentiation. 40, 99-105 (1989). PMID: 2547683 [PubMed - indexed for MEDLINE]
  • [3] Gunasekaran, K, "et al". PROTEINS: Structure, Function, and Bioinformatics. PMID: 14696180
  • [4] Marcelino, A, "et al". PROTEINS: Structure, Function, and Bioinformatics. PMID: 16477649 [Pubmed- indexed for MEDLINE]
  • [5] Xiao, H. and I. A. Kaltashov,J Am Soc Mass Spectrom. 16(6),869-79 (2005). | doi:10.1016/j.jasms.2005.02.020
  • [6] Krishnan, V. et al. Biochemistry 39(31), 9119-9129 (2000)PMID: 10924105 [PubMed - indexed for MEDLINE]
  • [7] Sacchettini, J. et al. J Biol Chem. 267(33), 23534-23545 (1992)
  • [8] Hodsdon, al. Biochemistry. 36(6), 1450-60(1997)| doi:10.1021/bi961890r
  • [9] Sjoelund, V. et al. Biochemistry.46, 13382–13390 (2007) | doi: 10.1021/bi700867c

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