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• W1972823428 abstract "We have mined the evolutionary record for the large family of intracellular lipid-binding proteins (iLBPs) by calculating the statistical coupling of residue variations in a multiple sequence alignment using methods developed by Ranganathan and coworkers (Lockless and Ranganathan, Science 1999:286;295-299). The 213 sequences analyzed have a wide range of ligand-binding functions as well as highly divergent phylogenetic origins, assuring broad sampling of sequence space. Emerging from this analysis were two major clusters of coupled residues, which when mapped onto the structure of a representative iLBP under study in our laboratory, cellular retinoic-acid binding protein I, are largely contiguous and provide useful points of comparison to available data for the folding of this protein. One cluster comprises a predominantly hydrophobic core away from the ligand-binding site and likely represents key structural information for the iLBP fold. The other cluster includes the portal region where ligand enters its binding site, regions of the ligand-binding cavity, and the region where the 10-stranded beta-barrel characteristic of this family closes (between strands 1' and 10). Linkages between these two clusters suggest that evolutionary pressures on this family constrain structural and functional sequence information in an interdependent fashion. The necessity of the structure to wrap around a hydrophobic ligand confounds the typical sequestration of hydrophobic side chains. Additionally, ligand entry and exit require these structures to have a capacity for specific conformational change during binding and release. We conclude that an essential and structurally apparent separation of local and global sequence information is conserved throughout the iLBP family." @default.
• W1972823428 created "2016-06-24" @default.
• W1972823428 creator A5009621753 @default.
• W1972823428 creator A5027934900 @default.
• W1972823428 creator A5081367513 @default.
• W1972823428 date "2006-02-13" @default.
• W1972823428 modified "2023-10-14" @default.
• W1972823428 title "Evolutionary coupling of structural and functional sequence information in the intracellular lipid-binding protein family" @default.
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• W1972823428 doi "https://doi.org/10.1002/prot.20860" @default.
• W1972823428 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16477649" @default.
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