Common structural features of cholesterol binding sites in crystallized soluble proteins

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Abstract Cholesterol-protein interactions are essential for the architectural organization of cell membranes and for lipid metabolism. While cholesterol-sensing motifs in transmembrane proteins have been identified, little is known about cholesterol recognition by soluble proteins. We reviewed the structural characteristics of binding sites for cholesterol and cholesterol sulfate from crystallographic structures available in the Protein Data Bank. This analysis unveiled key features of cholesterol-binding sites that are present in either all or the majority of sites: i) the cholesterol molecule is generally positioned between protein domains that have an organized secondary structure; ii) the cholesterol hydroxyl/sulfo group is often partnered by Asn, Gln, and/or Tyr, while the hydrophobic part of cholesterol interacts with Leu, Ile, Val, and/or Phe; iii) cholesterol hydrogen-bonding partners are often found on -helices, while amino acids that interact with cholesterol’s hydrophobic core have a slight preference for -strands and secondary structure-lacking protein areas; iv) the steroid’s C21 and C26 constitute the “hot spots” most often seen for steroid-protein hydrophobic interactions; v) common “cold spots” are C8–C10, C13, and C17, at which contacts with the proteins were not detected. Several common features we identified for soluble protein-steroid interaction appear evolutionarily conserved.—Bukiya, A. N., and A. M. Dopico. Common structural features of cholesterol binding sites in crystallized soluble proteins.

Original languageEnglish (US)
Pages (from-to)1044-1054
Number of pages11
JournalJournal of lipid research
Volume58
Issue number6
DOIs
StatePublished - Jun 1 2017

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Binding Sites
Cholesterol
Proteins
Steroids
Secondary Protein Structure
Common Cold
Hydrogen Bonding
Membrane Lipids
Hydrophobic and Hydrophilic Interactions
Lipid Metabolism
Hydroxyl Radical
Hydrogen bonds
Databases
Amino Acids
Molecules

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Common structural features of cholesterol binding sites in crystallized soluble proteins. / Bukiya, Anna; Dopico, Alejandro.

In: Journal of lipid research, Vol. 58, No. 6, 01.06.2017, p. 1044-1054.

Research output: Contribution to journalReview article

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AB - Abstract Cholesterol-protein interactions are essential for the architectural organization of cell membranes and for lipid metabolism. While cholesterol-sensing motifs in transmembrane proteins have been identified, little is known about cholesterol recognition by soluble proteins. We reviewed the structural characteristics of binding sites for cholesterol and cholesterol sulfate from crystallographic structures available in the Protein Data Bank. This analysis unveiled key features of cholesterol-binding sites that are present in either all or the majority of sites: i) the cholesterol molecule is generally positioned between protein domains that have an organized secondary structure; ii) the cholesterol hydroxyl/sulfo group is often partnered by Asn, Gln, and/or Tyr, while the hydrophobic part of cholesterol interacts with Leu, Ile, Val, and/or Phe; iii) cholesterol hydrogen-bonding partners are often found on -helices, while amino acids that interact with cholesterol’s hydrophobic core have a slight preference for -strands and secondary structure-lacking protein areas; iv) the steroid’s C21 and C26 constitute the “hot spots” most often seen for steroid-protein hydrophobic interactions; v) common “cold spots” are C8–C10, C13, and C17, at which contacts with the proteins were not detected. Several common features we identified for soluble protein-steroid interaction appear evolutionarily conserved.—Bukiya, A. N., and A. M. Dopico. Common structural features of cholesterol binding sites in crystallized soluble proteins.

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