The high-resolution structure of the extracellular domain of human CD69 using a novel polymer

Kolenko, Petr; Skálová, Tereza; Vaněk, Ondřej; Štěpánková, Andrea; Dušková, Jarmila; Hašek, Jindřich; Bezouška, Karel; Dohnálek, Jan

doi:10.1107/s1744309109043152

Cited by 17 publications

(17 citation statements)

References 17 publications

(16 reference statements)

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“…Thus, the structural variance between the single chains of mClr-g and hCD69 is approximately on the same level as the structural difference between chains A and B in one dimer of mClr-g or hCD69. RMSD of C a atoms of the complete dimers is much higher (2.4 Å , superposition of 229 residues "dimer to dimer," hCD69, PDB code 3HUP) (34). This indicates that the global fold of a monomer main chain is preserved more rigorously than is the assembly of the dimer.…”

Section: Discussionmentioning

confidence: 95%

Mouse Clr-g, a Ligand for NK Cell Activation Receptor NKR-P1F: Crystal Structure and Biophysical Properties

Skálová

Kotýnková

Dušková

et al. 2012

The Journal of Immunology

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Interactions between C-type lectin-like NK cell receptors and their protein ligands form one of the key recognition mechanisms of the innate immune system that is involved in the elimination of cells that have been malignantly transformed, virally infected, or stressed by chemotherapy or other factors. We determined an x-ray structure for the extracellular domain of mouse C-type lectin related (Clr) protein g, a ligand for the activation receptor NKR-P1F. Clr-g forms dimers in the crystal structure resembling those of human CD69. This newly reported structure, together with the previously determined structure of mouse receptor NKR-P1A, allowed the modeling and calculations of electrostatic profiles for other closely related receptors and ligands. Despite the high similarity among Clr-g, Clr-b, and human CD69, these molecules have fundamentally different electrostatics, with distinct polarization of Clr-g. The electrostatic profile of NKR-P1F is complementary to that of Clr-g, which suggests a plausible interaction mechanism based on contacts between surface sites of opposite potential.

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Section: Discussionmentioning

confidence: 95%

Mouse Clr-g, a Ligand for NK Cell Activation Receptor NKR-P1F: Crystal Structure and Biophysical Properties

Skálová

Kotýnková

Dušková

et al. 2012

The Journal of Immunology

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“…The X-ray diffraction data set was collected on the beamline NW12A of the Photon Factory (Tsukuba, Japan). Using the diffraction data, the LLT1 structure was solved by the molecular replacement method, with the crystal structure of CD69 (PDB ID: 3HUP) [32] as a search model. The model of LLT1 was refined until the value of R and R free factors converged using refinement programs.…”

Section: Resultsmentioning

confidence: 99%

“…The structure was determined by the molecular replacement method with the program BALBES in the CCP4 suite [40], using the structure of CD69 (PDB ID: 3HUP) [32] as a search model. Rotation and translation functions were calculated using data from 50.0 to 2.5Å resolution.…”

Section: Structure Determination Of Llt1mentioning

confidence: 99%

Crystal structure of extracellular domain of human lectin‐like transcript 1 (LLT1), the ligand for natural killer receptor‐P1A

et al. 2015

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Emerging evidence has revealed the pivotal roles of C-type lectin-like receptors (CTLRs) in the regulation of a wide range of immune responses. Human natural killer cell receptor-P1A (NKRP1A) is one of the CTLRs and recognizes another CTLR, lectin-like transcript 1 (LLT1) on target cells to control NK, NKT and Th17 cells. The structural basis for the NKRP1A-LLT1 interaction was limitedly understood. Here, we report the crystal structure of the ectodomain of LLT1. The plausible receptor-binding face of the C-type lectin-like domain is flat, and forms an extended β-sheet. The residues of this face are relatively conserved with another CTLR, keratinocyte-associated C-type lectin, which binds to the CTLR member, NKp65. A LLT1-NKRP1A complex model, prepared using the crystal structures of LLT1 and the keratinocyte-associated C-type lectin-NKp65 complex, reasonably satisfies the charge consistency and the conformational complementarity to explain a previous mutagenesis study. Furthermore, crystal packing and analytical ultracentrifugation revealed dimer formation, which supports a complex model. Our results provide structural insights for understanding the binding modes and signal transduction mechanisms, which are likely to be conserved in the CTLR family, and for further rational drug design towards regulating the LLT1 function.Keywords: Cell surface receptor r Crystal structure r C-type lectin-like receptor r Natural killer cell r Protein-protein interactions Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Prof. Katsumi Maenaka e-mail: maenaka@pharm.hokudai.ac.jp * Equal contribution.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 1606 S. Kita et al. Eur. J. Immunol. 2015. 45: 1605-1613 Introduction Natural killer (NK) cells are a component of innate immunity, and display cytotoxic activities against tumor cells and virally infected cells [1,2]. The activities of NK cells are precisely regulated by activating and inhibitory signals, through diverse receptors on the cell surface [3][4][5]. These receptors are encoded in two genomic regions, the leukocyte receptor complex (chromosome 19 in human) [6] and the NK gene complex (chromosome 12 in human) [7,8]. The leukocyte receptor complex encodes the NK receptors of the immunoglobulin (Ig) superfamily, such as killer Ig-like receptors and leukocyte Ig-like receptors, whereas the NK gene complex region encodes the NK receptors of the C-type lectinlike receptors (CTLRs). The CTLRs are subdivided into two groups, according to their expression patterns. Killer cell lectin-like receptors (KLRs) are expressed in NK cells, and C-type lectin receptors (CLECs) are expressed in non-NK cells [9]. The ligands of KLRs are (1) major histocompatibility complex (MHC) class I molecules and relatives, and (2) CLECs. The former members include CD94, the NKG2 subfamily [10], and the Ly49 subfamily [11], and the latter members are the NK receptor-P1 (NKRP1) subfamily [12,13]. The NKRP1 su...

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“…To better understand the structural basis for the specificity of the binding to CD161, we generated structural representations of the three CLEC2D isoforms. The model for LLT1 was generated based on the crystal structure of CD69, the closest homologue of LLT1 (13,20). As shown in Fig.…”

Section: Clec2d Protein Isoform 1 (Llt1) Is the Only Ligand Of Cd161mentioning

confidence: 99%

Characterization of Alternatively Spliced Transcript Variants of CLEC2D Gene

Germain

Bihl²,

Zahn³

et al. 2010

Journal of Biological Chemistry

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Lectin-like transcript 1 (LLT1) encoded by CLEC2D gene is a C-type lectin-like molecule interacting with human CD161 (NKR-P1A) receptor expressed by natural killer cells and subsets of T cells. Using RT-PCR and sequencing, we identified several CLEC2D alternatively spliced transcript variants generated by exon skipping. In addition to the reported transcript variants 1 (LLT1) and 2, we identified a novel splice variant 4 and transcripts coding for putative soluble proteins. CLEC2D transcripts were detected primarily in hematopoietic cell lines and were found to be co-induced by the same activation signals. Although very low amounts of putative soluble CLEC2D protein isoforms could be produced by transfectants, CLEC2D isoforms 2 and 4 were efficiently expressed. By contrast to LLT1, which was detected on the cell surface, isoform 2 and 4 remained in the endoplasmic reticulum where they formed homodimers or heterodimers with LLT1. They failed to interact with CD161, leaving LLT1 as the sole ligand for this receptor. CLEC2D therefore uses gene splicing to generate protein isoforms that are structurally distinct and that have different biological activities.

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The high-resolution structure of the extracellular domain of human CD69 using a novel polymer

Cited by 17 publications

References 17 publications

Mouse Clr-g, a Ligand for NK Cell Activation Receptor NKR-P1F: Crystal Structure and Biophysical Properties

Mouse Clr-g, a Ligand for NK Cell Activation Receptor NKR-P1F: Crystal Structure and Biophysical Properties

Crystal structure of extracellular domain of human lectin‐like transcript 1 (LLT1), the ligand for natural killer receptor‐P1A

Characterization of Alternatively Spliced Transcript Variants of CLEC2D Gene

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