PDBsum entry 1c3a

Membrane protein

PDB id

1c3a

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Contents

			Protein chains

					135 a.a. *


					125 a.a. *

			Waters ×93

* Residue conservation analysis

PDB id:

1c3a

Links

Name:

Membrane protein

Title:

Crystal structure of flavocetin-a from the habu snake venom, a novel cyclic tetramer of c-type lectin-like heterodimers

Structure:

Flavocetin-a: alpha subunit. Chain: a. Flavocetin-a: beta subunit. Chain: b

Source:

Trimeresurus flavoviridis. Organism_taxid: 88087. Other_details: trimeresurus flavoviridis. Other_details: trimeresurus flavoviridis

Biol. unit:

Dimer (from PDB file)

Resolution:

2.50Å

R-factor:

0.208

R-free:

0.269

Authors:

K.Fukuda,H.Mizuno,H.Atoda,T.Morita

Key ref:

K.Fukuda et al. (2000). Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers. Biochemistry, 39, 1915-1923. PubMed id: 10684640 DOI: 10.1021/bi992134z

Date:

27-Jul-99

Release date:

06-Mar-00

PROCHECK

	Headers

	References

Protein chain

Q8AV97 (SLAA_PROFL) - Snaclec flavocetin-A subunit alpha from Protobothrops flavoviridis

Seq: Struc:					158 a.a. 135 a.a.*

Protein chain

Q8AV98 (SLAB_PROFL) - Snaclec flavocetin-A subunit beta from Protobothrops flavoviridis

Seq: Struc:					148 a.a. 125 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1021/bi992134z	Biochemistry 39:1915-1923 (2000)
PubMed id: 10684640

Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers.
K.Fukuda, H.Mizuno, H.Atoda, T.Morita.

ABSTRACT

Snake venom contains a number of the hemostatically active C-type lectin-like proteins, which affect the interaction between von Willebrand factor (vWF) and the platelet glycoprotein (GP) Ib or platelet receptor to inhibit/induce platelet activation. Flavocetin-A (FL-A) is a high-molecular mass C-type lectin-like protein (149 kDa) isolated from the habu snake venom. FL-A binds with high affinity to the platelet GP Ibalpha-subunit and functions as a strong inhibitor of vWF-dependent platelet aggregation. We have determined the X-ray crystal structure of FL-A and refined to 2.5 A resolution. This is a first elucidation of a three-dimensional structure of the platelet GP Ib-binding protein. The overall structure reveals that the molecule is a novel cyclic tetramer (alphabeta)(4) made up of four alphabeta-heterodimers related by a crystallographic 4-fold symmetry. The tetramerization is mediated by an interchain disulfide bridge between cysteine residues at the C-terminus of the alpha-subunit and at the N-terminus of the beta-subunit in the neighboring alphabeta-heterodimer. The high affinity of FL-A for the platelet GP Ib alpha-subunit could be explained by a cooperative-binding action through the multiple binding sites of the tetramer.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21256857

Z.Chen, J.Wu, Y.Zhang, X.Yang, G.Yu, S.Zhu, W.Lee, Q.Lu, and Y.Zhang (2011).
A novel platelet glycoprotein Ib-binding protein with human platelet aggregation-inhibiting activity from Trimeresurus jerdonii venom.

Toxicon, 57, 672-679.

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

18221359

C.H.Chang, C.H.Chung, H.L.Kuo, C.C.Hsu, and T.F.Huang (2008).
The highly specific platelet glycoprotein (GP) VI agonist trowaglerix impaired collagen-induced platelet aggregation ex vivo through matrix metalloproteinase-dependent GPVI shedding.

J Thromb Haemost, 6, 669-676.

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

16689765

K.Kato, K.Furihata, Y.Cheli, G.Radis-Baptista, and T.J.Kunicki (2006).
Effect of multimer size and a natural dimorphism on the binding of convulxin to platelet glycoprotein (GP)VI.

J Thromb Haemost, 4, 1107-1113.

16782791

P.J.Kundrotas, and E.Alexov (2006).
Electrostatic properties of protein-protein complexes.

Biophys J, 91, 1724-1736.

16206329

A.Bazaa, N.Marrakchi, M.El Ayeb, L.Sanz, and J.J.Calvete (2005).
Snake venomics: comparative analysis of the venom proteomes of the Tunisian snakes Cerastes cerastes, Cerastes vipera and Macrovipera lebetina.

Proteomics, 5, 4223-4235.

15585533

E.Zhao, H.L.Liu, C.H.Tsai, H.K.Tsai, C.H.Chan, and C.Y.Kao (2005).
Cysteine separations profiles on protein sequences infer disulfide connectivity.

Bioinformatics, 21, 1415-1420.

16508096

G.Xu, Q.Huang, M.Teng, P.Liu, Y.Dong, and L.Niu (2005).
Crystallization and preliminary X-ray crystallographic analysis of agkicetin-C from Deinagkistrodon acutus venom.

Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 75-78.

15863880

S.Sugawara, M.Hosono, Y.Ogawa, M.Takayanagi, and K.Nitta (2005).
Molecular and sugar-binding heterogeneity of C-type lectins from Osmerus (Spirinchus) lanceolatus eggs.

Biol Pharm Bull, 28, 791-796.

15502319

G.Xu, M.Teng, L.Niu, P.Liu, Y.Dong, Q.Liu, Q.Huang, and Q.Hao (2004).
Purification, characterization, crystallization and preliminary X-ray crystallographic analysis of two novel C-type lectin-like proteins: Aall-A and Aall-B from Deinagkistrodon acutus venom.

Acta Crystallogr D Biol Crystallogr, 60, 2035-2037.

14684891

T.Batuwangala, M.Leduc, J.M.Gibbins, C.Bon, and E.Y.Jones (2004).
Structure of the snake-venom toxin convulxin.

Acta Crystallogr D Biol Crystallogr, 60, 46-53.

PDB code:

1uos

15005338

T.Morita (2004).
Use of snake venom inhibitors in studies of the function and tertiary structure of coagulation factors.

Int J Hematol, 79, 123-129.

12945044

C.C.Chuang, C.Y.Chen, J.M.Yang, P.C.Lyu, and J.K.Hwang (2003).
Relationship between protein structures and disulfide-bonding patterns.

Proteins, 53, 1-5.

13129929

E.Laurine, C.Grégoire, M.Fändrich, S.Engemann, S.Marchal, L.Thion, M.Mohr, B.Monsarrat, B.Michel, C.M.Dobson, E.Wanker, M.Erard, and J.M.Verdier (2003).
Lithostathine quadruple-helical filaments form proteinase K-resistant deposits in Creutzfeldt-Jakob disease.

J Biol Chem, 278, 51770-51778.

14580195

K.Horii, D.Okuda, T.Morita, and H.Mizuno (2003).
Structural characterization of EMS16, an antagonist of collagen receptor (GPIa/IIa) from the venom of Echis multisquamatus.

Biochemistry, 42, 12497-12502.

PDB code:

1ukm

14501123

M.T.Murakami, L.Watanabe, L.M.Gava, S.P.Zela, A.C.Cintra, and R.K.Arni (2003).
Initial structural analysis of an alpha4beta4 C-type lectin from the venom of Crotalus durissus terrificus.

Acta Crystallogr D Biol Crystallogr, 59, 1813-1815.

12851390

N.Maita, K.Nishio, E.Nishimoto, T.Matsui, Y.Shikamoto, T.Morita, J.E.Sadler, and H.Mizuno (2003).
Crystal structure of von Willebrand factor A1 domain complexed with snake venom, bitiscetin: insight into glycoprotein Ibalpha binding mechanism induced by snake venom proteins.

J Biol Chem, 278, 37777-37781.

PDB code:

1uex

11914494

S.Liu, Z.Zhu, J.Sun, Z.Zhu, Q.Huang, M.Teng, and L.Niu (2002).
Purification, crystallization and preliminary X-ray crystallographic analysis of agkaggregin, a C-type lectin-like protein from Agkistrodon acutus venom.

Acta Crystallogr D Biol Crystallogr, 58, 675-678.

12130642

X.Y.Du, J.M.Clemetson, A.Navdaev, E.M.Magnenat, T.N.Wells, and K.J.Clemetson (2002).
Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI.

J Biol Chem, 277, 35124-35132.

11148028

U.Sen, S.Vasudevan, G.Subbarao, R.A.McClintock, R.Celikel, Z.M.Ruggeri, and K.I.Varughese (2001).
Crystal structure of the von Willebrand factor modulator botrocetin.

Biochemistry, 40, 345-352.

PDB code:

1fvu

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.