Department of Physical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
Chromosome Dynamics Laboratory, RIKEN, Wako, Saitama, Japan.
EMBO Rep. 2019 May;20(5). doi: 10.15252/embr.201847183. Epub 2019 Mar 11.
Condensin I is a multi-protein complex that plays an essential role in mitotic chromosome assembly and segregation in eukaryotes. It is composed of five subunits: two SMC (SMC2 and SMC4), a kleisin (CAP-H), and two HEAT-repeat (CAP-D2 and CAP-G) subunits. Although balancing acts of the two HEAT-repeat subunits have been demonstrated to enable this complex to support the dynamic assembly of chromosomal axes in vertebrate cells, its underlying mechanisms remain poorly understood. Here, we report the crystal structure of a human condensin I subcomplex comprising hCAP-G and hCAP-H. hCAP-H binds to the concave surfaces of a harp-shaped HEAT-repeat domain of hCAP-G. Physical interaction between hCAP-G and hCAP-H is indeed essential for mitotic chromosome assembly recapitulated in egg cell-free extracts. Furthermore, this study reveals that the human CAP-G-H subcomplex has the ability to interact with not only double-stranded DNA, but also single-stranded DNA, suggesting functional divergence of the vertebrate condensin I complex in proper mitotic chromosome assembly.
结构凝缩蛋白 I 是一种多蛋白复合物，在真核生物有丝分裂染色体的组装和分离中发挥着重要作用。它由五个亚基组成：两个 SMC（SMC2 和 SMC4）、一个 kleisin（CAP-H）和两个 HEAT-repeat（CAP-D2 和 CAP-G）亚基。尽管已经证明两个 HEAT-repeat 亚基的平衡作用使该复合物能够支持脊椎动物细胞中染色体轴的动态组装，但其潜在机制仍知之甚少。在这里，我们报告了一个由 hCAP-G 和 hCAP-H 组成的人结构凝缩蛋白 I 亚复合物的晶体结构。hCAP-H 结合在 hCAP-G 的 harp 形状的 HEAT-repeat 结构域的凹面。hCAP-G 和 hCAP-H 之间的物理相互作用对于在卵细胞无细胞提取物中重新组装的有丝分裂染色体组装确实是必不可少的。此外，这项研究表明，人类 CAP-G-H 亚复合物不仅能够与双链 DNA 相互作用，还能够与单链 DNA 相互作用，这表明脊椎动物结构凝缩蛋白 I 复合物在适当的有丝分裂染色体组装中具有功能分化。
