SEQUENCE-ANALYSIS AND CHROMOSOMAL LOCALIZATION OF HUMAN CAP-Z - CONSERVED RESIDUES WITHIN THE ACTIN-BINDING DOMAIN MAY LINK CAP-Z TO GELSOLIN/SEVERIN AND PROFILIN PROTEIN FAMILIES
SEQUENCE-ANALYSIS AND CHROMOSOMAL LOCALIZATION OF HUMAN CAP-Z - CONSERVED RESIDUES WITHIN THE ACTIN-BINDING DOMAIN MAY LINK CAP-Z TO GELSOLIN/SEVERIN AND PROFILIN PROTEIN FAMILIES
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DOI：
10.1074/jbc.270.37.21472
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发表时间：
1995-09-15
影响因子：
4.8
通讯作者：
CASELLA, JF
中科院分区：
文献类型：
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作者：
BARRONCASELLA, EA;TORRES, MA;CASELLA, JF
从人视网膜 cDNA 文库中，我们分离出与鸡 Cap Z 的 α 2 和 β 亚基同源的 cDNA。衍生的人 α 亚基与鸡 α 2 亚基具有 95% 的氨基酸同一性； β 亚基与鸡亚基残基 1-243 具有 99% 的同一性。人 β 亚基的其余部分 (244-272) 存在显着差异，两个物种之间 29 个 C 端氨基酸中只有 8 个是保守的。这种保守性的缺乏特别令人感兴趣，因为鸡 C 端含有肌动蛋白结合结构域。F-肌动蛋白的共沉淀测定表明，人 Cap Z 与肌动蛋白的亲和力等于鸡 Cap Z 的亲和力。这些结果表明，八个共享氨基酸对于肌动蛋白结合至关重要，其中三个是它们是规则间隔的亮氨酸，这些非极性残基和分歧区域外的一个残基与针对凝溶胶蛋白片段 1 提出的肌动蛋白结合 α 螺旋的残基很好地对齐。非极性残基以及三个极性氨基酸在其他加帽、加帽和切断以及单体结合蛋白中也保守。两个最高度保守的亮氨酸的鸡 β 亚基中的氨基酸取代导致 F-肌动蛋白显着减少结合活性，人类 α 2 基因 (CAPZA2) 已定位到 7 号染色体位置 q31.2-q31.3，β 基因 (CAPZB) 定位到 1 号染色体区域 p36.1。
From a human retinal cDNA library, we have isolated cDNAs that are homologs for the alpha 2 and beta subunits of chicken Cap Z. The derived human alpha subunit shares 95% amino acid identity with the chicken alpha 2 subunit; the beta subunit is 99% identical to the chicken subunit residues 1-243. The remaining portion of the human beta subunit (244-272) diverges significantly with only 8 out of 29 C-terminal amino acids conserved between the two species, This lack of conservation is of particular interest because the chicken C terminus contains an actin-binding domain, Cosedimentation assays with F-actin show that human Cap Z binds actin with an affinity equal that of chicken Cap Z, These results point to the eight shared amino acids as critical for actin binding, three of which are regularly spaced leucines, These apolar residues and one outside the region of divergence align well with those residues of the actin-binding alpha-helix proposed for gelsolin segment 1. The apolar residues as well as three polar amino acids are also conserved in other capping, capping and severing, and monomer-binding proteins, Amino acid substitutions in the chicken beta subunit of the two most highly conserved leucines result in significant decreases in F-actin binding activity, The human alpha 2 gene (CAPZA2) has been mapped to chromosome 7 position q31.2-q31.3 and the beta gene (CAPZB) to chromosome 1 region p36.1.