Structural and functional characterization of natural killer cell receptors

Sun, Peter D.

Abstract

The function of natural killer (NK) and myeloid cells depends on the balance of a number of activating and inhibitory receptors. Natural cytotoxicity receptors (NCR) are the major receptors responsible for NK cell-mediated lysis of tumor and viral-infected cells. In the past few years, we have characterized the structure and function of several inhibitory as well as activating NK cell receptors. These include the crystal structures of CD94, KIR2DL2 and its complex with HLA-Cw3, NKG2D and its complex with ULBP3, NKp46 and TREM-1. Despite the progress made in understanding the function of NK receptors in the past few years, the ligands recognized by NCR remain unknown. Our effort of understanding the function of NCR has led a structural solution for NKp30. The structure revealed striking resemblence between NKp30 and CTLA-4 family receptors and enabled us to propose a potential ligand binding site.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAAI000697-19
• Application #: 8555804
• Support Year: 19
• Fiscal Year: 2012
• Total Cost: $313,099

Institution

• Name: National Institute of Allergy and Infectious Diseases

Publications

Spencer, Matthew; Max, Nathan; Ireland, Joanna et al. (2017) Over-expression of a human CD62L ecto-domain and a potential role of RNA pseudoknot structures in recombinant protein expression. Protein Expr Purif 140:65-73

Zou, Zhongcheng; Misasi, John; Sullivan, Nancy et al. (2017) Overexpression of Ebola virus envelope GP1 protein. Protein Expr Purif 135:45-53

Sim, Malcolm J W; Sun, Peter D (2017) HLA-F: A New Kid Licensed for Peptide Presentation. Immunity 46:972-974

Brown, Haley A; Roth, Gwynne; Holzapfel, Genevieve et al. (2015) Development of an improved mammalian overexpression method for human CD62L. Protein Expr Purif 105:8-13

Abdi, Kaveh; Singh, Nevil J; Spooner, Eric et al. (2014) Free IL-12p40 monomer is a polyfunctional adaptor for generating novel IL-12-like heterodimers extracellularly. J Immunol 192:6028-36

Lu, Jinghua; Sun, Peter D (2014) A rapid and rational approach to generating isomorphous heavy-atom phasing derivatives. FEBS J 281:4021-8

Lu, Jinghua; Yu, Yadong; Zhu, Iowis et al. (2014) Structural mechanism of serum amyloid A-mediated inflammatory amyloidosis. Proc Natl Acad Sci U S A 111:5189-94

Wang, Ruipeng; Sun, Peter D (2014) Natural killer cell-mediated shedding of ULBP2. PLoS One 9:e91133

Lu, Jinghua; Sun, Peter D (2012) The structure of the TLR5-flagellin complex: a new mode of pathogen detection, conserved receptor dimerization for signaling. Sci Signal 5:pe11

Joyce, M Gordon; Tran, Paul; Zhuravleva, Marina A et al. (2011) Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site. Proc Natl Acad Sci U S A 108:6223-8