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Cellular retinoic acid-binding protein: Difference between revisions

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New page: One of the CBI Molecules being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at ...
 
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<StructureSection load='' size='350' side='right' scene='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/1cbs_molecularplayground/20' caption='Cellular retinoic acid binding protein I (CRABP I) [[1cbs]]'>
 
One of the [[CBI Molecules]] being studied in the  [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
One of the [[CBI Molecules]] being studied in the  [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
<applet load='1cbs' size='400' color='white' frame='true' align='right' caption='Cellular retinoic acid binding protein I (CRABP I)'
scene='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/1cbs_molecularplayground/20'/>
<scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/1cbs_molecularplayground/20'>Molecular Playground: CRABP I</scene>
<scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/1cbs_molecularplayground/20'>Molecular Playground: CRABP I</scene>


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


__TOC__
==Function==


 
'''Cellular Retinoic Acid Binding Proteins''' ('''CRABPs''') are small intracellular proteins (15.5
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
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 [http://www.ncbi.nlm.nih.gov/pubmed/8756459?dopt=Abstract/]. During embryonic development, the spatial and temporal expression of the CRABP gene appears to be strictly regulated [http://www.ncbi.nlm.nih.gov/pubmed/2547683]. 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.  
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 [http://www.ncbi.nlm.nih.gov/pubmed/8756459?dopt=Abstract/]. During embryonic development, the spatial and temporal expression of the CRABP gene appears to be strictly regulated [http://www.ncbi.nlm.nih.gov/pubmed/2547683]. 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. '''Epididymal RABP (ERABP)''' is an androgen-dependent RABP present in the lumen of the epididymis believed to be involved in sperm maturation.  ERABP binds specifically all-trans- and 9-cis-RA.  
==Structure==
*'''CRABP I''' is expressed during embryogenesis and also in adult tissues.
*'''CRABP II''' is expressed in skin embryogenesis.
*'''CRABP IV''' promotes oxidative stress by decreasing endothelial mitochondrial function.


Proteins in iLBP family have very high structural conservation despite having very low sequence identities [http://www.ncbi.nlm.nih.gov/pubmed/14696180]. Similar to other members of the iLBP family, <scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/Monomercrabpi/2'>CRABP I</scene> [http://www.pdb.org/pdb/explore/explore.do?structureId=1CBI (PDBID: 1CBI)] has two orthogonal five-stranded <scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/Monomercrabpi/4'> β-sheets</scene> with a <scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/Monomercrabpi/19'>helix-turn-helix</scene> between the first and the second β-strands,showing &alpha;+&beta;
secondary domains.  It contains a very large solvent accessible central cavity that binds <scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/1cbs_molecularplayground/5'>retinoic acid</scene> [http://www.pdb.org/pdb/explore/explore.do?structureId=1CBS (PDBID: 1CBS)].  This conserved <scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/Monomercrabpi/6'>gap</scene> 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 <scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/Monomercrabpi/7'>'lid'</scene> on the ligand binding pocket.  Strands 7 and 8 are connected by the <scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/Monomercrabpi/9'>omega loop</scene> which has variable lengths within the family.  There are 15 fully <scene name='CRABP_I_(_Cellular_Retinoic_Acid_Binding_Protein_)/Monomercrabpi/10'>conserved</scene> residues in CRABP I, seven are found in the helix I and II and 5 are in the β-barrel closure [http://www.ncbi.nlm.nih.gov/pubmed/16477649].
==Structure==
==Structure==


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of CRABPs is proposed to occur via a region of the protein comprising determinants
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 [http://pubs.acs.org/doi/abs/10.1021/bi961890r].
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 [http://pubs.acs.org/doi/abs/10.1021/bi961890r].
==3D structure of cellular retinoic acid-binding protein==
[[Cellular retinoic acid-binding protein 3D structures]]
</StructureSection>


==See Also==
==See Also==


* [http://en.wikipedia.org/wiki/CRABP1 Cellular retinoic acid-binding protein 1 at Wikipedia]
* [http://en.wikipedia.org/wiki/CRABP1 Cellular retinoic acid-binding protein 1 at Wikipedia]
* [http://www.rcsb.org/pdb/explore/explore.do?structureId=1CBI apo-CRABP I ( PDB ID ; 1CBI) at RCSB PDB]
* [http://www.rcsb.org/pdb/explore/explore.do?structureId=1CBR holo-CRABP I ( PDB ID ; 1CBR) at RCSB PDB]
* [http://www.pdb.org/pdb/explore/explore.do?structureId=1CBS ( PDB ID ; 1CBS) at RCSB PDB]
==3D structure of Cellular retinoic acid-binding protein==
===CRABP I===
[[2cbr]] - hCRABP I – human<br />
[[1cbr]] - CRABP  I + retinoic acid – mouse
===CRABP II===
[[2fs6]], [[2fs7]] - hCRABP II<br />
[[1blr]] - hCRABP II – NMR<br />
[[3fek]], [[3fel]], [[3fen]], [[3fa7]], [[3fa8]], [[3fa9]], [[3i17]], [[3d95]], [[3d96]], [[3d97]], [[2frs]] - hCRABP II (mutant) <br />
[[3f8a]], [[3f9d]], [[3fa6]], [[3cr6]], [[2g79]], [[2g7b]] – hCRABP II (mutant) + retinal analog<br />
[[3cwk]], [[2g78]] – hCRABP II (mutant) + retinoic acid<br />
[[2fr3]], [[2cbs]], [[3cbs]], [[1cbq]], [[1cbs]] – hCRABP II + retinoic acid<br />
[[3fep]] - hCRABP II (mutant) + ligand


==References==
==References==
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*[8] Hodsdon, M.''et al''.  Biochemistry. 36(6), 1450-60(1997)| doi:10.1021/bi961890r
*[8] Hodsdon, M.''et 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
*[9] Sjoelund, V. ''et al''. Biochemistry.46, 13382–13390 (2007) | doi: 10.1021/bi700867c
[[Category:Topic Page]]

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Michal Harel, Alexander Berchansky
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