Peter Sun, Ph.D.

Peter D. Sun, Ph.D.

Credit: NIAID

Major Areas of Research

  • Structural immunology
  • Structure and function of NK-cell receptors
  • Structural mechanisms of HIV and host interactions

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Program Description

Structure and ligand recognition of NK-cell receptors

Natural killer (NK) cells constitute an important branch of host innate immunity against tumor and viral infection. The activation of NK cells is controlled by the balance of activating and inhibitory receptors, To understand the molecular mechanism of NK-cell target recognition, we have carried out structural studies on a number of activating and inhibitory NK-cell receptors. As examples of the activating receptors, we determined the crystal structures of NKG2D in complex with its ligand ULBP3 and of a natural cytotoxicity receptor (NCR) NKp46. To gain functional insights into the inhibitory NK receptors, we determined the crystal structures of human CD94, KIRDL2 and its complex with a class I MHC ligand, HLA-Cw3. Through these structural works, from both our lab and others', we learned how NK cells recognize their ligands. We continue our structural studies on the natural cytotoxicity receptors and their ligand identification.

Structural mechanism of HIV-1 and host interactions

HIV type 1 (HIV-1) infects macrophages efficiently despite relatively low levels of cell-surface CD4 expression. Additional attachment factors on host cells have been suggested to facilitate the viral entry. We have studied HIV-1 envelope gp120 interaction with host carbohydrate receptors, such as DC-SIGN, in the past few years. While DC-SIGN binds gp120 with high affinity, it does not appear to facilitate the viral entry. Instead, our preliminary results showed that HIV-1 gp120 recognized, both in solution and on cell surface, a new family of myeloid-lineage carbohydrate receptors, the Sialic acid-binding immunoglobulin-like lectins (Siglec) through envelope-associated sialic acids. We are currently investigating the functional relevance of gp120-Siglec recognition, whether HIV-1 uses Siglecs to facilitate its host entry, and the potential importance of envelope carbohydrates in HIV infection and pathogenesis.

HIV-1 encodes an accessory protein, vpu, to facilitate the maturation and efficient host cell release of viral particles. Recently, CD317 has been identified as a host target of vpu and renamed tetherin, for its ability to retain HIV-1 viral particles on transfected cells. The gene for tetherin, also known as bone marrow stromal antigen 2 (BST2), encodes a 180-amino acid type II transmembrane protein with a predicted GPI-anchor at the c-terminus. Evidence suggests that tetherin induces the internalization of nascent virus to endocytic compartments, thus inhibiting their release, and the expression of vpu promotes the intracellular degradation of tetherin.

While this recent work provides significant insight into vpu and tetherin interactions and their role in viral release, the mechanism of tetherin-mediated viral retention as seen in vpu infection remains unclear. In particular, what is the viral target of tetherin and how does tetherin interact with HIV-1 and inhibit virus release? To address these questions, we propose to investigate the structure and function of tetherin by X-ray crystallography and identify its HIV-1 viral ligands using solution and cell surface binding approaches. These studies will not only advance our understanding of HIV-1 biology and viral pathogenesis but also facilitate the design of potential novel tetherin mimics to help sequester and clear the virus from infected individuals.

Fc receptor recognition by immunoglobulins and pentraxins

Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component (SAP) and C-reactive protein (CRP), which are parts of acute-phase proteins synthesized in response to infection. Both recognize microbial pathogens and activate the classical complement pathway through C1q. More recently, members of the pentraxin family were found to interact with cell surface Fcγ receptors (FcγR) and activate leukocyte-mediated phagocytosis 5-8. We now describe the structural mechanism for pentraxin binding to FcγR and its functional activation of FcγR-mediated phagocytosis and cytokine secretion. The complex structure between human SAP and FcγRIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. The 1:1 stoichiometry between SAP and FcγRIIa infers the requirement for multivalent pathogen binding for receptor aggregation. Mutational and binding studies show that pentraxins are diverse in their binding specificity to FcγR isoforms but conserved in their recognition structure. The shared binding site for SAP and IgG results in competition for FcγR binding and the inhibition of immune complex-mediated phagocytosis by soluble pentraxins. These results establish the antibody-like functions for pentraxins in the FcγR pathway, suggest an evolutionary overlap between the innate and adaptive immune systems, and have novel therapeutic implications for autoimmune diseases.


Dr. Sun obtained his Ph.D. from the Molecular Biology Institute, University of Oregon, for the study of structure and thermostability of phage T4 lysozyme using X-ray crystallography. He then joined the National Institute of Diabetes and Digestive and Kidney DIseases for his postdoctoral training in 1991, focusing on the structure and function of cytokines. In particular, he determined the crystal structure of a human transforming growth factor, TGF-beta 2. He joined NIAID in 1994.

Research Group

Peter Sun (Structural Immunology Section) Research Group

Front row (left to right): Peter Sun, Joanna Ireland, Genevieve Holzapfel, Gwynne Roth, Zhongcheng (Ted) Zou, Jinghua Lu. Back row (left to right): Joseph Kononchik, Nathan Max, Matthew Spencer, Ruipeng Wang.



(View complete listing in PubMed.)

Joyce MG, Tran P, Zhuravleva MA, Jaw J, Colonna M, Sun PD. Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6223-8.

Lu J, Marjon KD, Marnell LL, Wang R, Mold C, Du Clos TW, Sun P. Recognition and functional activation of the human IgA receptor (Fc{alpha}RI) by C-reactive protein. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4974-9.

Radaev S, Zou Z, Tolar P, Nguyen K, Nguyen A, Krueger PD, Stutzman N, Pierce S, Sun PD. Structural and functional studies of Igalphabeta and its assembly with the B cell antigen receptor. Structure. 2010 Aug 11;18(8):934-43.

Bivona L, Zou Z, Stutzman N, Sun PD. Influence of the second amino acid on recombinant protein expression. Protein Expr Purif. 2010 Dec;74(2):248-56.

Radaev S, Zou Z, Huang T, Lafer EM, Hinck AP, Sun PD. Ternary complex of transforming growth factor-beta1 reveals isoform-specific ligand recognition and receptor recruitment in the superfamily. J Biol Chem. 2010 May 7;285(19):14806-14.

Joyce MG, Radaev S, Sun PD. A rational approach to heavy-atom derivative screening. Acta Crystallogr D Biol Crystallogr. 2010 Ap;66(Pt 4):358-65.

Tools & Equipment

Rigaku X-ray generators

Rigaku X-ray generators

Computer room

Computer room

Chemical and biological hoods

Chemical and biological hoods

Laboratory space

Laboratory space

Sub-zero freezers

Sub-zero freezers


X-ray Equipment

  • 2 Rigaku X-ray generators
  • 1 Raxis IV imaging plate detector
  • 1 Raxis IV++ imaging plate detector
  • 2 LN2 cryogenic systems

Laboratory Equipment

  • Gilson HPLC
  • Biocad 700E
  • Pharmacia FPLC
  • Bioflo 3000 Bioreactor
  • Microscopes

Computer Equipment

  • 2 SGI O2s running IRIX3
  • 8 PCs running Red Hat Enterprise Linux 5/6
  • 1 Tektronix Phaser 440 printer
  • 3 HP LaserJet printers

Crystallosgraphic Software

  • CCP4
  • Phaser
  • Phenix
  • Solve/Resolve
  • Pymol
  • CCP4MG
  • XtalView
  • Coot
  • HKL2000
  • Arp Warp
  • Doc
  • Dtrek
  • Shelx
  • Sharp
  • SnB
  • O
  • Phases
  • CNS
  • APBS
  • TNT
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