Crystal structure and functional implication of the RUN domain of human NESCA

Protein Cell. 2012 Aug;3(8):609-17. doi: 10.1007/s13238-012-2052-3. Epub 2012 Jul 22.


NESCA, a newly discovered signaling adapter protein in the NGF-pathway, contains a RUN domain at its N-terminus. Here we report the crystal structure of the NESCA RUN domain determined at 2.0-Å resolution. The overall fold of the NESCA RUN domain comprises nine helices, resembling the RUN domain of RPIPx and the RUN1 domain of Rab6IP1. However, compared to the other RUN domains, the RUN domain of NESCA has significantly different surface electrostatic distributions at the putative GTPase-interacting interface. We demonstrate that the RUN domain of NESCA can bind H-Ras, a downstream signaling molecule of TrkA, with high affinity. Moreover, NESCA RUN can directly interact with TrkA. These results provide new insights into how NESCA participates in the NGF-TrkA signaling pathway.

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
  • Crystallography, X-Ray
  • Gene Expression
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Growth Factor / chemistry*
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Oncogene Protein p21(ras) / chemistry*
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptor, trkA / chemistry*
  • Receptor, trkA / genetics
  • Receptor, trkA / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • rab GTP-Binding Proteins / chemistry


  • Adaptor Proteins, Signal Transducing
  • DENND5A protein, human
  • Guanine Nucleotide Exchange Factors
  • RUSC1 protein, human
  • Recombinant Proteins
  • Nerve Growth Factor
  • Receptor, trkA
  • Oncogene Protein p21(ras)
  • rab GTP-Binding Proteins