气候变化领域集成服务门户(CCPortal): Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules

CCPortal

DOI	10.1073/pnas.1706483114
	Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules
	Blázquez-Moreno A.; Park S.; Im W.; Call M.J.; Call M.E.; Reyburn H.T.
发表日期	2017
ISSN	0027-8424
起始页码	E5645
结束页码	E5654
卷号	114 期号:28
英文摘要	Many activating immunoreceptors associate with signaling adaptor molecules like FcϵR1γ or CD247. FcϵR1γ and CD247 share high sequence homology and form disulphide-linked homodimers that contain a pair of acidic aspartic acid residues in their transmembrane (TM) domains that mediate assembly, via interaction with an arginine residue at a similar register to these aspartic acids, with the activating immunoreceptors. However, this model cannot hold true for receptors like CD16A, whose TM domains do not contain basic residues. We have carried out an extensive site-directed mutagenesis analysis of the CD16A receptor complex and now report that the association of receptor with the signaling adaptor depends on a network of polar and aromatic residues along the length of the TM domain. Molecular modeling indicates that CD16A TM residues F202, D205, and T206 form the core of the membrane-embedded trimeric interface by establishing highly favorable contacts to the signaling modules through rearrangement of a hydrogen bond network previously identified in the CD247 TM dimer solution NMR structure. Strikingly, the amino acid D205 also regulates the turnover and surface expression of CD16A in the absence of FcϵR1γ or CD247. Modeling studies indicate that similar features underlie the association of other activating immune receptors, including CD64 and FcϵR1α, with signaling adaptor molecules, and we confirm experimentally that equivalent F, D, and T residues in the TM domain of FcϵR1α markedly influence the biology of this receptor and its association with FcϵR1γ.
英文关键词	Activating immunoreceptors; Fc receptors; Signaling adaptor molecules; Transmembrane interactions
语种	英语
scopus关键词	amino acid; CD16A antigen; CD247 antigen; CD64 antigen; Fc epsilon receptor 1 alpha; Fc epsilon receptor 1 gamma; Fc receptor; signal transducing adaptor protein; unclassified drug; CD3 antigen; CD3 antigen, zeta chain; Fc receptor; FCGR3B protein, human; glycosylphosphatidylinositol anchored protein; immunoglobulin E receptor; immunoglobulin receptor; Article; cell surface; complex formation; controlled study; human; human cell; hydrogen bond; molecular dynamics; molecular model; nuclear magnetic resonance spectroscopy; priority journal; protein domain; protein expression; protein function; protein structure; regulatory mechanism; signal transduction; site directed mutagenesis; transmembrane domain; turnover time; animal; cell line; cell membrane; glycosylation; HEK293 cell line; metabolism; mouse; protein domain; protein motif; protein multimerization; Amino Acid Motifs; Animals; CD3 Complex; Cell Line; Cell Membrane; Glycosylation; GPI-Linked Proteins; HEK293 Cells; Humans; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Mice; Mutagenesis, Site-Directed; Protein Domains; Protein Multimerization; Receptors, IgE; Receptors, IgG; Receptors, Immunologic; Signal Transduction
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160616
作者单位	Blázquez-Moreno, A., Department of Immunology and Oncology, Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas, Madrid, 28049, Spain; Park, S., Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, United States, Bioengineering Program, Lehigh University, Bethlehem, PA 18015, United States; Im, W., Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, United States, Bioengineering Program, Lehigh University, Bethlehem, PA 18015, United States; Call, M.J., Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia, Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Call, M.E., Structural Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia, Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Reyburn, H.T., Department of Immunology and Oncology, Centro Nac...
推荐引用方式 GB/T 7714	Blázquez-Moreno A.,Park S.,Im W.,et al. Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules[J],2017,114(28).
APA	Blázquez-Moreno A.,Park S.,Im W.,Call M.J.,Call M.E.,&Reyburn H.T..(2017).Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules.Proceedings of the National Academy of Sciences of the United States of America,114(28).
MLA	Blázquez-Moreno A.,et al."Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules".Proceedings of the National Academy of Sciences of the United States of America 114.28(2017).