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Modes of Cholesterol Binding in Membrane Proteins: A Joint Analysis of 73 Crystal Structures

  • Cong Wang
  • Arthur Ralko
  • Zhong Ren
  • Avia Rosenhouse-Dantsker
  • Xiaojing YangEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1135)

Abstract

Cholesterol is a highly asymmetric lipid molecule. As an essential constituent of the cell membrane, cholesterol plays important structural and signaling roles in various biological processes. The first high-resolution crystal structure of a transmembrane protein in complex with cholesterol was a human β2-adrenergic receptor structure deposited to the Protein Data Bank in 2007. Since then, the number of the cholesterol-bound crystal structures has grown considerably providing an invaluable resource for obtaining insights into the structural characteristics of cholesterol binding. In this work, we examine the spatial and orientation distributions of cholesterol relative to the protein framework in a collection of 73 crystal structures of membrane proteins. To characterize the cholesterol-protein interactions, we apply singular value decomposition to an array of interatomic distances, which allows us to systematically assess the flexibility and variability of cholesterols in transmembrane proteins. Together, this joint analysis reveals the common characteristics among the observed cholesterol structures, thereby offering important guidelines for prediction and modification of potential cholesterol binding sites in transmembrane proteins.

Keywords

Crystal structure Membrane protein Cholesterol-protein interactions Singular value decomposition Distance matrix 

Abbreviations

CARC

Inverted CRAC

CCM

Cholesterol consensus motif

CLR

Cholesterol

CRAC

Cholesterol recognition amino acid consensus

GPCR

G-protein coupled receptor

PDB

Protein Data Bank

RMSD

Root mean square deviation

SVD

Singular value decomposition

TM

Transmembrane

VDW

van del Waals

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Cong Wang
    • 1
  • Arthur Ralko
    • 1
  • Zhong Ren
    • 1
  • Avia Rosenhouse-Dantsker
    • 1
  • Xiaojing Yang
    • 1
    • 2
    Email author
  1. 1.Department of ChemistryUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of Ophthalmology and Vision SciencesUniversity of Illinois at ChicagoChicagoUSA

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