Cited by 11Lipid Membrane Structure and BehaviorProtein Structure and DynamicsReceptor Mechanisms and Signaling

Critical residues and motifs for homodimerization of the first transmembrane domain of the plasma membrane glycoprotein CD36

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Wei, Peng, Sun, Fu-de, Zuo, Li-min, Qu, Jing, Chen, Peng, Xu, Li-da, Luo, Shi-Zhong·2017·Journal of Biological Chemistry

Abstract

The plasma transmembrane (TM) glycoprotein CD36 is critically involved in many essential signaling processes, especially the binding/uptake of long-chain fatty acids and oxidized low-density lipoproteins. The association of CD36 potentially activates cytosolic protein tyrosine kinases that are thought to associate with the C-terminal cytoplasmic tail of CD36. To understand the mechanisms by which CD36 mediates ligand binding and signal transduction, we have characterized the homo-oligomeric interaction of CD36 TM domains in membrane environments and with molecular dynamics (MD) simulations. Analysis of pyrene- and coumarin-labeled TM1 peptides in SDS by FRET confirmed the homodimerization of the CD36 TM1 peptide. Homodimerization assays of CD36 TM domains with the TOXCAT technique showed that its first TM (TM1) domain, but not the second TM (TM2) domain, could homodimerize in a cell membrane. Small-residue, site-specific mutation scanning revealed that the CD36 TM1 dimerization is mediated by the conserved small residues Gly 12 , Gly 16 , Ala 20 , and Gly 23 . Furthermore, molecular dynamics (MD) simulation studies demonstrated that CD36 TM1 exhibited a switching dimerization with two right-handed packing modes driven by the 12 G XXX G XXX A 20 and 20 A XX G 23 motifs, and the mutational effect of G16I and G23I revealed these representative conformations of CD36 TM1. This packing switch pattern of CD36 TM1 homodimer was further examined and confirmed by FRET analysis of monobromobimane (mBBr)-labeled CD36 TM1 peptides. Overall, this work provides a structural basis for understanding the role of TM association in regulating signal transduction via CD36.

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  • Adipocytes promote macrophage recruitment, then adipocytes and immune cells secrete more adipokines such as leptin, chemerin, resistin, and more cytokines such as TNF-α, ILs, INF-γ, creating a circumstance of low-grade inflammation.

    “Specifically, adipocytes promote macrophage recruitment (21), then adipocytes and immune cells secrete more adipokines such as leptin, chemerin, resistin, and more cytokines such as tumor necrosis factor-α (TNF-α), interleukins (ILs), interferon-γ (INF-γ) (22–25), creating a circumstance of low-grade inflammation.”

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Authors
Wei, P., Sun, F.-D., Zuo, L.-M., Qu, J., Chen, P., Xu, L.-D., & Luo, S.-Z.
Affiliations
  • Beijing University of Chinese Medicine (CN)
  • Beijing University of Chemical Technology (CN)
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2017-05
Volume
292
Issue
21
Pages
8683-8693
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2598883265
Cited by
11
References
69
Citations by year
2024: 3 · 2023: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 3
FWCI
0.56
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Basic Research Program of China (2013CB910700)
  • National Natural Science Foundation of China (21372026, 61304147, 21672019)
  • Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
CD36, transmembrane domain, homodimerization, plasma membrane glycoproteins, critical residues, ligand binding, fatty acid uptake, signal transduction, protein tyrosine kinase activation, fluorescence resonance energy transfer, molecular dynamics simulation, site-directed mutagenesis
MeSH terms
Protein Domains, Humans, CD36 Antigens, Amino Acid Motifs, Protein Structure, Quaternary, Protein Multimerization, Molecular Dynamics Simulation

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