Structural analysis of intermolecular interactions in the kinesin adaptor complex fasciculation and elongation protein zeta 1/ short coiled-coil protein (FEZ1/SCOCO)

PLoS One. 2013 Oct 7;8(10):e76602. doi: 10.1371/journal.pone.0076602. eCollection 2013.

Abstract

Cytoskeleton and protein trafficking processes, including vesicle transport to synapses, are key processes in neuronal differentiation and axon outgrowth. The human protein FEZ1 (fasciculation and elongation protein zeta 1 / UNC-76, in C. elegans), SCOCO (short coiled-coil protein / UNC-69) and kinesins (e.g. kinesin heavy chain / UNC116) are involved in these processes. Exploiting the feature of FEZ1 protein as a bivalent adapter of transport mediated by kinesins and FEZ1 protein interaction with SCOCO (proteins involved in the same path of axonal growth), we investigated the structural aspects of intermolecular interactions involved in this complex formation by NMR (Nuclear Magnetic Resonance), cross-linking coupled with mass spectrometry (MS), SAXS (Small Angle X-ray Scattering) and molecular modelling. The topology of homodimerization was accessed through NMR (Nuclear Magnetic Resonance) studies of the region involved in this process, corresponding to FEZ1 (92-194). Through studies involving the protein in its monomeric configuration (reduced) and dimeric state, we propose that homodimerization occurs with FEZ1 chains oriented in an anti-parallel topology. We demonstrate that the interaction interface of FEZ1 and SCOCO defined by MS and computational modelling is in accordance with that previously demonstrated for UNC-76 and UNC-69. SAXS and literature data support a heterotetrameric complex model. These data provide details about the interaction interfaces probably involved in the transport machinery assembly and open perspectives to understand and interfere in this assembly and its involvement in neuronal differentiation and axon outgrowth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Binding Sites / genetics
  • Biological Transport
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Humans
  • Kinesins
  • Magnetic Resonance Spectroscopy
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Scattering, Small Angle
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • X-Ray Diffraction

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • FEZ1 protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Recombinant Proteins
  • SCOC protein, human
  • Kinesins

Grants and funding

This research was financially supported by Fundação de Amparo à Pesquisa do Estado São Paulo (http://www.fapesp.br/), the Conselho Nacional de Pesquisa e Desenvolvimento (http://www.cnpq.br/; through a personal grant to JK: 471355/2010-0) and Centro Nacional de Pesquisa em Energia e Materiais / Laboratório Nacional de Biociências (http://www.lnbio.org.br/site/home.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.