Crystal structure of EMS16 in complex with the integrin alpha2-I domain.
Snake venoms contain a number of heterodimeric C-type lectin-like proteins (CLPs) that interact specifically with components of the haemostatic system. EMS16 from the venom of Echis multisquamatus binds to the collagen receptor, integrin alpha2beta1, also known as glycoprotein (GP) Ia/IIa, and specifically inhibits collagen binding. Here we report the crystal structure of EMS16 in complex with recombinant integrin alpha2-I domain that plays a central role in collagen binding. The structure of the complex at 1.9 Angstrom resolution reveals that the collagen-binding site of the alpha2-I domain is covered completely by the bound EMS16. This blockage by EMS16 appears to spatially inhibit collagen binding to the alpha2-I domain. The bound alpha2-I domain adopts a closed conformation, which is seen in the absence of ligand, suggesting that EMS16 stabilizes a closed conformation corresponding to the less active structure of the alpha2-I domain. EMS16 does not directly bind to the manganese ion and residues of the metal ion-dependent adhesion site (MIDAS) of the alpha2-I domain, suggesting that EMS16 may have the potential to bind specifically to the alpha2-I domain in a metal ion-independent fashion.
Horii
Katsunori
K
Department of Biochemistry, National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan.
Okuda
Daiju
D
Morita
Takashi
T
Mizuno
Hiroshi
H
D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014757:Viper Venoms / Q000737:chemistry* / Q000378:metabolism*
C412704:EMS16 lectin, Echis multisquamtus; D038982:Integrin alpha2beta1; D037181:Lectins, C-Type; D014757:Viper Venoms