Miron T, Wilchek M, Geiger B
Department of Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Eur J Biochem. 1988 Dec 15;178(2):543-53. doi: 10.1111/j.1432-1033.1988.tb14481.x.
We report here on the purification and characterization of a new 25-kDa inhibitor of actin polymerization from turkey gizzard smooth muscle. The protein was purified by chromatography on DEAE-cellulose and hydroxyapatite, as well as by affinity chromatography on an immobilized-antibody column. The purified polypeptide reduced the low-shear viscosity of actin, apparently due to its inhibitory effect on actin polymerization. We demonstrate that this protein is largely responsible for the apparent inhibitory activity previously reported to be associated with smooth muscle vinculin preparations. Three independent monoclonal antibodies prepared against the 25-kDa inhibitor of actin polymerization can effectively adsorb the inhibiting activity of actin polymerization from the crude vinculin preparation or inhibit it. We also show here that the 25-kDa inhibitor of actin polymerization tends to undergo dimerization when maintained in non-reducing buffers, concomitant with the loss of its inhibitory activity. Immunohistochemical labeling of frozen sections, as well as immunoblotting analyzes, indicated that the 25-kDa inhibitor of actin polymerization is particularly enriched in smooth muscle cells and that its distribution is apparently homogenous throughout the cytoplasm showing no apparent enrichment in the vinculin-rich dense plaques located along the endofacial surface of the plasma membrane.
我们在此报告从火鸡砂囊平滑肌中纯化和鉴定一种新的25 kDa肌动蛋白聚合抑制剂。该蛋白通过DEAE - 纤维素和羟基磷灰石色谱法以及固定化抗体柱上的亲和色谱法进行纯化。纯化的多肽降低了肌动蛋白的低剪切粘度,这显然是由于其对肌动蛋白聚合的抑制作用。我们证明这种蛋白质在很大程度上负责先前报道的与平滑肌纽蛋白制剂相关的明显抑制活性。针对25 kDa肌动蛋白聚合抑制剂制备的三种独立单克隆抗体可以有效地从粗纽蛋白制剂中吸附肌动蛋白聚合的抑制活性或抑制它。我们还在此表明,当保持在非还原缓冲液中时,25 kDa肌动蛋白聚合抑制剂倾向于发生二聚化,同时其抑制活性丧失。冷冻切片的免疫组织化学标记以及免疫印迹分析表明,25 kDa肌动蛋白聚合抑制剂在平滑肌细胞中特别富集,并且其分布在整个细胞质中明显均匀,在沿质膜内表面定位的富含纽蛋白的致密斑中没有明显富集。