title: Molecular dynamic simulation of the self-assembly of DAP12-NKG2C activating immunoreceptor complex.
abstract: The DAP12-NKG2C activating immunoreceptor complex is one of the multisubunit transmembrane protein complexes in which ligand-binding receptor chains assemble with dimeric signal-transducing modules through non-covalent associations in their transmembrane (TM) domains. In this work, both coarse grained and atomistic molecular dynamic simulation methods were applied to investigate the self-assembly dynamics of the transmembrane domains of the DAP12-NKG2C activating immunoreceptor complex. Through simulating the dynamics of DAP12-NKG2C TM heterotrimer and point mutations, we demonstrated that a five-polar-residue motif including: 2 Asps and 2 Thrs in DAP12 dimer, as well as 1 Lys in NKG2C TM plays an important role in the assembly structure of the DAP12-NKG2C TM heterotrimer. Furthermore, we provided clear evidences to exclude the possibility that another NKG2C could stably associate with the DAP12-NKG2C heterotrimer. Based on the simulation results, we proposed a revised model for the self-assembly of DAP12-NKG2C activating immunoreceptor complex, along with a plausible explanation for the association of only one NKG2C with a DAP12 dimer.
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Lida
authors.initials: L
authors.lastname: Xu
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Cheng-Dong
authors.initials: CD
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Fu-De
authors.initials: FD
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Tan
authors.affiliation: Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P. R. China.
authors.forename: Shi-Zhong
authors.initials: SZ
authors.lastname: Luo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D055654:NK Cell Lectin-Like Receptor Subfamily C; C110546:TYROBP protein, human