Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow - 226 001, India.
J Struct Biol. 2010 Dec;172(3):219-24. doi: 10.1016/j.jsb.2010.07.001. Epub 2010 Jul 11.
Leishmania donovani ADF/cofilin (LdCof) is a novel member of ADF/cofilin family. LdCof depolymerizes, but does not co-sediment with, rabbit muscle actin filaments. Its F-actin depolymerizing activity is pH independent. Further, it possesses weak F-actin severing activity. In order to better understand its characteristic properties, we have determined the solution NMR structure of LdCof and have analyzed protein backbone dynamics from (15)N-relaxation measurements. The structure of LdCof possesses a conserved ADF/cofilin fold with a central mixed β-sheet consisting of six β-strands which is surrounded by five α-helices. LdCof structure has conserved G/F-actin binding site which includes the characteristic long kinked α-helix (α3). LdCof binds to rabbit muscle ADP-G-actin with 1:1 stoichiometry (K(d)∼0.2μM). The F-actin binding site is not well formed and analysis of (15)N-relaxation data shows that residues in the β4-β5 loop region and C-terminal are relatively flexible, which seems to be a determinant for the low F-actin severing activity of LdCof.
杜氏利什曼原虫 ADF/cofilin（LdCof）是 ADF/cofilin 家族的一个新成员。LdCof 可解聚但不解聚兔肌动蛋白丝。其 F-肌动蛋白解聚活性与 pH 无关。此外，它还具有较弱的 F-肌动蛋白切割活性。为了更好地理解其特征性质，我们已经确定了 LdCof 的溶液 NMR 结构，并通过（15）N 弛豫测量分析了蛋白质骨架动力学。LdCof 的结构具有保守的 ADF/cofilin 折叠，其中央混合β-片层由六个β-链组成，周围有五个α-螺旋。LdCof 结构具有保守的 G/F-肌动蛋白结合位点，其中包括特征性的长弯曲α-螺旋（α3）。LdCof 与兔肌 ADP-G-肌动蛋白以 1:1 的化学计量比结合（Kd∼0.2μM）。F-肌动蛋白结合位点未完全形成，（15）N 弛豫数据分析表明，β4-β5 环区和 C 末端的残基相对灵活，这似乎是 LdCof 低 F-肌动蛋白切割活性的决定因素。
