Characterization of the interaction between beta2-glycoprotein I and calmodulin, and identification of a binding sequence in beta2-glycoprotein I.
beta2-Glycoprotein I was shown to bind reversibly to calmodulin in a Ca2+-dependent manner with a 1:1 stoichiometry, a Kd of 3 x 10(-9) M and a Hill coefficient of 1.4. A sequence in beta2-glycoprotein I (Lys-Pro-Gly-Tyr-Val-Ser-Arg-Gly-Gly-Met-Arg-Lys-Phe-Ile-) limited by Cys-32 and Cys-47 is suggested to be the calmodulin-binding region. This sequence was the only one in beta2-glycoprotein I theoretically having the ability to form a basic amphiphilic alpha-helix typical of a calmodulin binding sequence. The peptide corresponding to this sequence was synthesized and found to inhibit the interaction between beta2-glycoprotein I and calmodulin with an IC50 value of 0.38 x [beta2-glycoprotein I] and to displace the beta2-glycoprotein I from the beta2-glycoprotein I/calmodulin complex with an IC50 value of 0.90 x [beta2-glycoprotein I].
Røjkjaer
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Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark.
Klaerke
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DA
Schousboe
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I
D000818:Animals; D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D006023:Glycoproteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011863:Radioimmunoassay; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry; D053482:beta 2-Glycoprotein I
D002147:Calmodulin; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I; D014364:Tryptophan