Crystal structure and functional implication of the RUN domain of human NESCA.
10.1007/s13238-012-2052-3
- Author:
Qifan SUN
1
;
Chuanhui HAN
;
Lan LIU
;
Yizhi WANG
;
Hongyu DENG
;
Lin BAI
;
Tao JIANG
Author Information
1. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
- Publication Type:Journal Article
- MeSH:
Adaptor Proteins, Signal Transducing;
chemistry;
genetics;
metabolism;
Amino Acid Sequence;
Binding Sites;
Crystallography, X-Ray;
Gene Expression;
Humans;
Models, Molecular;
Molecular Sequence Data;
Nerve Growth Factor;
chemistry;
genetics;
metabolism;
Oncogene Protein p21(ras);
chemistry;
genetics;
metabolism;
Protein Binding;
Protein Structure, Tertiary;
Receptor, trkA;
chemistry;
genetics;
metabolism;
Recombinant Proteins;
chemistry;
genetics;
metabolism;
Sequence Homology, Amino Acid;
Signal Transduction;
rab GTP-Binding Proteins;
chemistry
- From:
Protein & Cell
2012;3(8):609-617
- CountryChina
- Language:English
-
Abstract:
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.
