Backbone dynamics of the 8 kDa dynein light chain dimer reveals molecular basis of the protein's functional diversity

J Biomol NMR. 2002 Jun;23(2):103-14. doi: 10.1023/a:1016332918178.

Abstract

Axonemal and cytoplasmic dyneins share a highly conserved 8 kDa light chain (DLC8) for motor assembly and function. Other than serving as a light chain of dynein complexes, DLC8 has been shown to bind a larger number of proteins with diverse biological functions including cell cycle control, apoptosis, and cell polarity maintenance. Therefore, DLC8 is likely a multifunctional regulatory protein. DLC8 exists as a dimer in solution, and the protein dimer is capable of binding to two target molecules. In this work, the backbone dynamics of DLC8, both in its apo- and target-peptide bound forms, were characterized by 15N NMR relaxation studies. The relaxation data were analyzed using model-free approach. We show that the target peptide-binding region of apo-DLC8 experiences microsecond-to-millisecond time scale conformational fluctuation, suggesting that the target-binding region of the protein is capable of adjusting its shape and size in responding to its various targets. The conformational breathing of the target-binding region of apo-DLC8 was also supported by backbone amide exchange experiment. Such segmental conformational motion of the protein is significantly reduced upon forming a complex with a target peptide. The dynamic properties of DLC8 in solution provide insight into the protein's diverse sequence-dependent target binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoproteins / chemistry
  • Apoproteins / metabolism
  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Carrier Proteins / metabolism
  • Cytoplasmic Dyneins
  • Dimerization
  • Dyneins / chemistry*
  • Dyneins / metabolism*
  • Membrane Proteins*
  • Models, Molecular
  • Molecular Weight
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / metabolism
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins*
  • Rats
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Apoproteins
  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, rat
  • Carrier Proteins
  • Membrane Proteins
  • Peptides
  • Proto-Oncogene Proteins
  • Dynll1 protein, rat
  • Cytoplasmic Dyneins
  • Dyneins