Actin Filament Cross-linking by MARCKS
Actin Filament Cross-linking by MARCKS
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MARCKS 肌动蛋白丝交联
DOI：
--
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发表时间：
2001
影响因子：
4.8
通讯作者：
M. Bubb
中科院分区：
文献类型：
--
作者：
E. Yarmola;A. Edison;R. Lenox;M. Bubb
我们最近发现在肉豆油酰基化富丙氨酸蛋白激酶C底物（MARCKS）磷酸化时发生的构象变化妨碍了肌动蛋白丝的有效交联(Bubb, m.r., Lenox, r.h., and Edison, a.s. (1999) J. Biol。化学，274,36472-36478)。这些结果表明，MARCKS的磷酸化位点区域有两个肌动蛋白结合位点。我们现在提出的证据表明，存在两个肌动蛋白结合位点，它们不仅相互竞争，而且还与肌动蛋白结合蛋白胸腺酶β4和肌动蛋白结合蛋白特异性竞争，以结合肌动蛋白。在重复的六肽段中，丙氨酸取代苯丙氨酸的效果表明，该结构域的非带电区域有助于结合亲和力，但每个结合位点对应的肽的结合亲和力对盐浓度有很大的依赖性，这与假定的这些多阳离子肽与肌动蛋白的多阴离子N端之间的静电相互作用一致。磷酸化对位点特异性亲和力的降低不超过0.7 kcal/mol，小于丙氨酸取代的影响。然而，磷酸化比丙氨酸取代对肌动蛋白丝交联活性丧失的影响要大得多。这些结果与一种假设相一致，即由于磷酸化引起的构象变化导致的紧凑结构，以及位点特异性亲和力的适度降低，解释了磷酸化的marks中交联活性的丧失。
We recently identified conformational changes that occur upon phosphorylation of myristoylated alanine-rich protein kinase C substrate (MARCKS) that preclude efficient cross-linking of actin filaments (Bubb, M. R., Lenox, R. H., and Edison, A. S. (1999) J. Biol. Chem. 274, 36472–36478). These results implied that the phosphorylation site domain of MARCKS has two actin-binding sites. We now present evidence for the existence of two actin-binding sites that not only mutually compete but also specifically compete with the actin-binding proteins thymosin β4 and actobindin to bind to actin. The effects of substitution of alanine for phenylalanine within a repeated hexapeptide segment suggest that the noncharged region of the domain contributes to binding affinity, but the binding affinity of peptides corresponding to each binding site has a steep dependence on salt concentration, consistent with presumed electrostatic interactions between these polycationic peptides and the polyanionic N terminus of actin. Phosphorylation decreases the site-specific affinity by no more than 0.7 kcal/mol, which is less than the effect of alanine substitution. However, phosphorylation has a much greater effect than alanine substitution on the loss of actin filament cross-linking activity. These results are consistent with the hypothesis that the compact structure resulting from conformational changes due to phosphorylation, in addition to modest decreases in site-specific affinity, explains the loss of cross-linking activity in phosphorylated MARCKS.
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通过自缔合和肌动蛋白结合大分子交联肌动蛋白丝网络。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Griffith,LM;Pollard,TD
通讯作者：
Pollard,TD
DOI：
10.1073/pnas.84.20.7046
发表时间：
1987-10-01
影响因子：
11.1
作者：
ALBERT, KA;NAIRN, AC;GREENGARD, P
通讯作者：
GREENGARD, P
影响因子：
2.9
作者：
Kang, F;Laine, RO;Purich, DL
通讯作者：
Purich, DL
影响因子：
5.6
作者：
Wright, PE;Dyson, HJ
通讯作者：
Dyson, HJ
DOI：
10.1073/pnas.100139797
发表时间：
2000-06-06
影响因子：
11.1
作者：
Krucker, T;Siggins, GR;Halpain, S
通讯作者：
Halpain, S