Metzler W J, Farmer B T, Constantine K L, Friedrichs M S, Lavoie T, Mueller L
Department of Macromolecular NMR, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-400, USA.
Protein Sci. 1995 Mar;4(3):450-9. doi: 10.1002/pro.5560040312.
Profilin is a ubiquitous eukaryotic protein that binds to both cytosolic actin and the phospholipid phosphatidylinositol-4,5-bisphosphate. These dual competitive binding capabilities of profilin suggest that profilin serves as a link between the phosphatidyl inositol cycle and actin polymerization, and thus profilin may be an essential component in the signaling pathway leading to cytoskeletal rearrangement. The refined three-dimensional solution structure of human profilin I has been determined using multidimensional heteronuclear NMR spectroscopy. Twenty structures were selected to represent the solution conformational ensemble. This ensemble of structures has root-mean-square distance deviations from the mean structure of 0.58 A for the backbone atoms and 0.98 A for all non-hydrogen atoms. Comparison of the solution structure of human profilin to the crystal structure of bovine profilin reveals that, although profilin adopts essentially identical conformations in both states, the solution structure is more compact than the crystal structure. Interestingly, the regions that show the most structural diversity are located at or near the actin-binding site of profilin. We suggest that structural differences are reflective of dynamical properties of profilin that facilitate favorable interactions with actin. The global folding pattern of human profilin also closely resembles that of Acanthamoeba profilin I, reflective of the 22% sequence identity and approximately 45% sequence similarity between these two proteins.
丝切蛋白是一种普遍存在的真核生物蛋白，它既能结合胞质肌动蛋白，又能结合磷脂酰肌醇 - 4,5 - 二磷酸。丝切蛋白的这种双重竞争性结合能力表明，丝切蛋白在磷脂酰肌醇循环和肌动蛋白聚合之间起到连接作用，因此丝切蛋白可能是导致细胞骨架重排的信号通路中的一个重要组成部分。人类丝切蛋白I的精确三维溶液结构已通过多维异核核磁共振光谱法确定。选择了20个结构来代表溶液构象集合。该结构集合中，主链原子相对于平均结构的均方根距离偏差为0.58埃，所有非氢原子的均方根距离偏差为0.98埃。将人类丝切蛋白的溶液结构与牛丝切蛋白的晶体结构进行比较，结果表明，尽管丝切蛋白在两种状态下基本采用相同的构象，但溶液结构比晶体结构更紧凑。有趣的是，结构差异最大的区域位于丝切蛋白的肌动蛋白结合位点处或其附近。我们认为，结构差异反映了丝切蛋白的动态特性，这些特性有助于与肌动蛋白形成有利的相互作用。人类丝切蛋白的整体折叠模式也与棘阿米巴丝切蛋白I非常相似，这反映了这两种蛋白质之间22%的序列同一性和约45%的序列相似性。
