Crystal structure and functional implication of the RUN domain of human NESCA
Copyright policy )Crystal structure and functional implication of the RUN domain of human NESCA
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.
- Chinese Academy of Science (中国科学院) China (People's Republic of)
- Chinese Academy of Science China (People's Republic of)
- GRADUATE UNIVERSITY OF CHINESE ACADEMY OF SCIENCES China (People's Republic of)
- Chinese Academy of Sciences (中国科学院) China (People's Republic of)
- Institute of Biophysics China (People's Republic of)
Models, Molecular, Binding Sites, Sequence Homology, Amino Acid, Molecular Sequence Data, Gene Expression, Oncogene Protein p21(ras), Crystallography, X-Ray, Recombinant Proteins, Protein Structure, Tertiary, rab GTP-Binding Proteins, Nerve Growth Factor, Guanine Nucleotide Exchange Factors, Humans, Amino Acid Sequence, Receptor, trkA, Adaptor Proteins, Signal Transducing, Protein Binding, Signal Transduction
Models, Molecular, Binding Sites, Sequence Homology, Amino Acid, Molecular Sequence Data, Gene Expression, Oncogene Protein p21(ras), Crystallography, X-Ray, Recombinant Proteins, Protein Structure, Tertiary, rab GTP-Binding Proteins, Nerve Growth Factor, Guanine Nucleotide Exchange Factors, Humans, Amino Acid Sequence, Receptor, trkA, Adaptor Proteins, Signal Transducing, Protein Binding, Signal Transduction
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