Journal of the Korean Magnetic Resonance Society (한국자기공명학회논문지)

Korean Magnetic Resonance Society (한국자기공명학회)
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Recent advances in NMR-based structural characterization of αB-crystallin and its potential role in human diseases

  • Muniyappan, Srinivasan (Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology) ;
  • Kim, Jin Hae (Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology)
  • Received : 2019.03.18
  • Accepted : 2019.03.20
  • Published : 2019.03.20
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Abstract

${\alpha}B$-crystallin (${\alpha}BC$) is a member of a small heat-shock protein (sHSP) superfamily and plays a predominant role in cellular protein homeostasis network by rescuing misfolded proteins from irreversible aggregation. ${\alpha}BC$ assembles into dynamic and polydisperse high molecular weight complexes containing 12 to 48 monomers; this variable stereochemistry of ${\alpha}BC$ has been linked to quaternary subunit exchange and its chaperone activity. The chaperone activity of ${\alpha}BC$ poses great potential as therapeutic agents for various neurodegenerative diseases. In this mini-review, we briefly outline the recent advancement in structural characterization of ${\alpha}BCs$ and its potential role to inhibit protein misfolding and aggregation in various human diseases. In particular, nuclear magnetic resonance (NMR) spectroscopy and its complimentary techniques have contributed much to elucidate highly-dynamic nature of ${\alpha}BCs$, among which notable advancements are discussed in detail. We highlight the importance of resolving the structural details of various ${\alpha}BC$ oligomers, their quaternary dynamics, and structural heterogeneity.

Keywords

JGGMB2_2019_v23n1_26_f0001.png 이미지

Figure 1. Conformational model of αBC dimer in its 24-mer state (PDB 3J07).40 Each monomer is coloured blue or red, and the N- and C-terminal regions are removed for clear view (the residues 57-157 are only shown here). Note that two monomers adopt different conformations due to quaternary heterogeneity of αBC.

JGGMB2_2019_v23n1_26_f0002.png 이미지

Figure 2. Schematic representation of subunit exchange and quaternary dynamics of full-length human αBC (PDB 3J07), which is based on DA-SANS and ESI-nMS studies.37 The 24-mer complexes of αBC are shown in red and blue (left; before subunit exchange), while subunit exchange facilitates subunits to be mixed as shown with both colors present for each complex (right).

JGGMB2_2019_v23n1_26_f0003.png 이미지

Figure 3. Model for capturing amorphous and amyloid clients by full-length human αBC. For interaction with amorphous aggregates, the N-terminal domain (NTD) of αBC plays an essential role, while the β4-β8 binding groove of αBC constitutes the major interface to interact with amyloid aggregates. Reprinted by permission from Nature.30

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