Evidence for calmodulin inter-domain compaction in solution induced by W-7 binding

• Published in: FEBS letters Vol. 442; no. 2; pp. 173 - 177
• Main Authors: Osawa, Masanori, Kuwamoto, Shigeo, Izumi, Yoshinobu, Yap, Kyoko L, Ikura, Mitsuhiko, Shibanuma, Tadao, Yokokura, Hisayuki, Hidaka, Hiroyoshi, Matsushima, Norio
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.01.1999
• Subjects: Animals; Ca2+/CaM, calcium-bound CaM; Calcium - metabolism; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Calmodulin - chemistry; Calmodulin - metabolism; Calmodulin-W-7 complex; CaM, calmodulin; CaM-KII, Ca2+/CaM-dependent protein kinase II; Conformational change; CT-HSQC, constant time HSQC; DMSO, dimethyl sulfoxide; Globular structure; HSQC, heteronuclear single quantum coherence; Kinetics; MLCK, myosin light chain kinase; NMR, nuclear magnetic resonance; NOE, nuclear Overhauser enhancement; Nuclear Magnetic Resonance, Biomolecular; p(r), pair distance distribution function; Protein Binding; Protein Conformation - drug effects; R g, radius of gyration; SAXS, small-angle X-ray scattering; Small-angle X-ray scattering; Solutions; Sulfonamides - metabolism; Sulfonamides - pharmacology; TFP, trifluoperazine, 10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)-10H-phenothiazine; Trifluoperazine - chemistry; Trifluoperazine - metabolism; W-7, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; X-Ray Diffraction; Xenopus laevis; Globular structure; HSQC, heteronuclear single quantum coherence; CaM-KII, Ca 2+/CaM-dependent protein kinase II; TFP, trifluoperazine, 10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)-10 H-phenothiazine; SAXS, small-angle X-ray scattering; R g, radius of gyration; CaM, calmodulin; Calmodulin-W-7 complex; Conformational change; Small-angle X-ray scattering; W-7, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; NOE, nuclear Overhauser enhancement; NMR, nuclear magnetic resonance; p( r), pair distance distribution function; DMSO, dimethyl sulfoxide; CT-HSQC, constant time HSQC; MLCK, myosin light chain kinase; Ca 2+/CaM, calcium-bound CaM
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01637-8

Small-angle X-ray scattering and nuclear magnetic resonance were used to investigate the structural change of calcium-bound calmodulin (Ca 2+/CaM) in solution upon binding to its antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). The radius of gyration was 17.4±0.3 Å for Ca 2+/CaM-W-7 with a molar ratio of 1:5 and 20.3±0.7 Å for Ca 2+/CaM. Comparison of the radius of gyration and the pair distance distribution function of the Ca 2+/CaM-W-7 complex with those of other complexes indicates that binding of two W-7 molecules induces a globular shape for Ca 2+/CaM, probably caused by an inter-domain compaction. The results suggest a tendency for Ca 2+/CaM to form a globular structure in solution, which is inducible by a small compound like W-7.