School of Life and Environmental Sciences, The University of Sydney, NSW 2006, Australia.
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA; Biology Department, University of New Mexico, Albuquerque, NM 87131, USA.
Structure. 2016 Nov 1;24(11):2000-2007. doi: 10.1016/j.str.2016.08.018. Epub 2016 Oct 6.
The nuclear magnetic resonance (NMR) structure of the tri-helix bundle (THB) of the m-domain plus C2 (ΔmC2) of myosin-binding protein C (MyBP-C) has revealed a highly flexible seven-residue linker between the structured THB and C2. Bioinformatics shows significant patterns of conservation across the THB-linker sequence, with the linker containing a strictly conserved serine in all MyBP-C isoforms. Clinically linked mutations further support the functional significance of the THB-linker region. NMR, small-angle X-ray scattering, and binding studies show the THB-linker plus the first ten residues of C2 undergo dramatic changes when ΔmC2 binds Ca-calmodulin, with the linker and C2 N-terminal residues contributing significantly to the affinity. Modeling of all available experimental data indicates that the THB tertiary structure must be disrupted to form the complex. These results are discussed in the context of the THB-linker and the N-terminal residues of C2 forming a polymorphic binding domain that could accommodate multiple binding partners in the dynamic sarcomere.
肌球蛋白结合蛋白 C（MyBP-C）的 m 结构域加 C2（ΔmC2）的三螺旋束（THB）的核磁共振（NMR）结构揭示了结构 THB 和 C2 之间高度灵活的七残基接头。生物信息学显示，THB-接头序列在整个序列中具有显著的保守模式，接头中所有 MyBP-C 同工型都含有严格保守的丝氨酸。临床相关突变进一步支持了 THB-接头区域的功能意义。NMR、小角度 X 射线散射和结合研究表明，当 ΔmC2 结合 Ca-钙调蛋白时，THB-接头加 C2 的前十个残基会发生剧烈变化，接头和 C2 N 端残基对亲和力有重要贡献。对所有可用实验数据的建模表明，THB 三级结构必须被破坏才能形成复合物。这些结果在 THB-接头和 C2 的 N 端残基形成一个多态结合域的背景下进行了讨论，该域可以容纳动态肌节中的多个结合伴侣。
