Mazzoni M R, Hamm H E
Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago 60680.
J Protein Chem. 1993 Apr;12(2):215-21. doi: 10.1007/BF01026043.
The limited proteolytic pattern of transducin, Gt, and its purified subunits with chymotrypsin were analyzed and the cleavage sites on the alpha t subunit were identified. The alpha t subunit in the GTP gamma S bound form was cleaved into a major 38 kD fragment, whereas alpha t-GDP was progressively digested into 38, 23, 21, and 15 kD fragments. The beta gamma t subunit was not very sensitive to proteolytic digestion with chymotrypsin. The gamma t subunit was not cleaved and only a small portion of beta t was digested into several fragments. In order to determine which proteolytic fragment of alpha t still contained the carboxyl terminal region, chymotrypsinization was carried out using Gt previously 32P-labeled at Cys347 by pertussis toxin-catalyzed ADP-ribosylation. The 32P-label was mainly associated with the alpha t subunit and a 15 kD fragment. The 23 and 21 kD fragments were not 32P-labeled. Analysis of amino terminal sequences of 38, 21, and 15 kD proteolytic bands allowed the identification of the major cleavage sites. Chymotrypsin had two cleavage sites in the amino terminal region of alpha t, at Leu15 and Leu19. Chymotrypsin removed 15-19 amino acid residues from the amino terminus of alpha t, generating two peptides (38 kD) which comigrates in gel electrophoresis. Chymotrypsin also cleaved at Trp207 in a conformation-dependent manner. Trp207 of alpha t-GTP gamma S was resistant to proteolysis but alpha t-GDP and the 38 kD fragments of alpha t-GDP produced the 23 and 21 kD fragments, respectively, and a 15 kD fragment containing the carboxyl terminus.(ABSTRACT TRUNCATED AT 250 WORDS)
分析了转导素(Gt)及其纯化亚基经胰凝乳蛋白酶作用后的有限蛋白水解模式,并确定了αt亚基上的切割位点。结合GTPγS形式的αt亚基被切割成一个主要的38kD片段,而αt-GDP则逐渐被消化成38、23、21和15kD片段。βγt亚基对胰凝乳蛋白酶的蛋白水解消化不太敏感。γt亚基未被切割,只有一小部分βt被消化成几个片段。为了确定αt的哪个蛋白水解片段仍包含羧基末端区域,使用先前通过百日咳毒素催化的ADP-核糖基化在Cys347处进行32P标记的Gt进行胰凝乳蛋白酶消化。32P标记主要与αt亚基和一个15kD片段相关。23和21kD片段未被32P标记。对38、21和15kD蛋白水解条带的氨基末端序列分析确定了主要切割位点。胰凝乳蛋白酶在αt的氨基末端区域有两个切割位点,分别在Leu15和Leu19处。胰凝乳蛋白酶从αt的氨基末端去除15-19个氨基酸残基,产生两个在凝胶电泳中迁移率相同的肽段(38kD)。胰凝乳蛋白酶还以构象依赖的方式在Trp207处切割。αt-GTPγS的Trp207对蛋白水解有抗性,但αt-GDP和αt-GDP的38kD片段分别产生23和21kD片段,以及一个包含羧基末端的15kD片段。(摘要截断于250字)