PDBsum entry 2c6u

Lectin

PDB id

2c6u

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Contents

			Protein chain

					122 a.a. *

			Waters ×246

* Residue conservation analysis

PDB id:

2c6u

Links

Name:

Lectin

Title:

Crystal structure of human clec-2 (clec1b)

Structure:

Clec1b protein. Chain: a. Fragment: c-type lectin-like domain, residues 100-221. Synonym: clec-2, c-type lectin-like receptor-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell: peripheral blood mononuclear cells. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plyss.

Resolution:

1.60Å

R-factor:

0.161

R-free:

0.198

Authors:

A.A.Watson,J.Brown,C.A.O'Callaghan

Key ref:

A.A.Watson et al. (2007). The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2. J Biol Chem, 282, 3165-3172. PubMed id: 17132623

Date:

11-Nov-05

Release date:

20-Nov-06

PROCHECK

	Headers

	References

Protein chain

Q9P126 (CLC1B_HUMAN) - C-type lectin domain family 1 member B from Homo sapiens

Seq: Struc:					229 a.a. 122 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

	J Biol Chem 282:3165-3172 (2007)
PubMed id: 17132623

The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2.
A.A.Watson, J.Brown, K.Harlos, J.A.Eble, T.S.Walter, C.A.O'Callaghan.

ABSTRACT

The human C-type lectin-like molecule CLEC-2 is expressed on the surface of platelets and signaling through CLEC-2 causes platelet activation and aggregation. CLEC-2 is a receptor for the platelet-aggregating snake venom protein rhodocytin. It is also a newly identified co-receptor for human immunodeficiency virus type 1 (HIV-1). An endogenous ligand has not yet been identified. We have solved the crystal structure of the extracellular domain of CLEC-2 to 1.6-A resolution, and identified the key structural features involved in ligand binding. A semi-helical loop region and flanking residues dominate the surface that is available for ligand binding. The precise distribution of hydrophobic and electrostatic features in this loop will determine the nature of any endogenous ligand with which it can interact. Major ligand-induced conformational change in CLEC-2 is unlikely as its overall fold is compact and robust. However, ligand binding could induce a tilt of a 3-10 helical portion of the long loop region. Mutational analysis and surface plasmon resonance binding studies support these observations. This study provides a framework for understanding the effects of rhodocytin venom binding on CLEC-2 and for understanding the nature of likely endogenous ligands and will provide a basis for rational design of drugs to block ligand binding.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20193029

A.M.Kerrigan, and G.D.Brown (2010).
Syk-coupled C-type lectin receptors that mediate cellular activation via single tyrosine based activation motifs.

Immunol Rev, 234, 335-352.

20482880

C.Chaipan, I.Steffen, T.S.Tsegaye, S.Bertram, I.Glowacka, Y.Kato, J.Schmökel, J.Münch, G.Simmons, R.Gerardy-Schahn, and S.Pöhlmann (2010).
Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2.

Retrovirology, 7, 47.

20154219

C.E.Hughes, A.Y.Pollitt, J.Mori, J.A.Eble, M.G.Tomlinson, J.H.Hartwig, C.A.O'Callaghan, K.Fütterer, and S.P.Watson (2010).
CLEC-2 activates Syk through dimerization.

Blood, 115, 2947-2955.

19025564

C.Huysamen, and G.D.Brown (2009).
The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors.

FEMS Microbiol Lett, 290, 121-128.

19837675

T.L.Hsu, S.C.Cheng, W.B.Yang, S.W.Chin, B.H.Chen, M.T.Huang, S.L.Hsieh, and C.H.Wong (2009).
Profiling carbohydrate-receptor interaction with recombinant innate immunity receptor-Fc fusion proteins.

J Biol Chem, 284, 34479-34489.

18583525

A.A.Watson, J.A.Eble, and C.A.O'Callaghan (2008).
Crystal structure of rhodocytin, a ligand for the platelet-activating receptor CLEC-2.

Protein Sci, 17, 1611-1616.

PDB code:

2vrp

18215137

C.M.Christou, A.C.Pearce, A.A.Watson, A.R.Mistry, A.Y.Pollitt, A.E.Fenton-May, L.A.Johnson, D.G.Jackson, S.P.Watson, and C.A.O'Callaghan (2008).
Renal cells activate the platelet receptor CLEC-2 through podoplanin.

Biochem J, 411, 133-140.

18597489

E.Hooley, E.Papagrigoriou, A.Navdaev, A.V.Pandey, J.M.Clemetson, K.J.Clemetson, and J.Emsley (2008).
The crystal structure of the platelet activator aggretin reveals a novel (alphabeta)2 dimeric structure.

Biochemistry, 47, 7831-7837.

PDB code:

3bx4

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.