Structural basis of human cytoglobin for ligand binding.
Structural basis of human cytoglobin for ligand binding.
复制标题
DOI：
10.1016/j.jmb.2004.04.024
复制
发表时间：
2004-06
影响因子：
5.6
通讯作者：
H. Sugimoto;M. Makino;H. Sawai;N. Kawada;K. Yoshizato;Y. Shiro
中科院分区：
文献类型：
--
作者：
H. Sugimoto;M. Makino;H. Sawai;N. Kawada;K. Yoshizato;Y. Shiro
细胞珠蛋白（Cgb）是脊椎动物珠蛋白家族的一个新成员，与其他哺乳动物的血红蛋白（Hb）、肌红蛋白（Mb）和神经珠蛋白（Ngb）一样，通过血红素可逆地与O 2结合。虽然Cgb在各种组织中表达，但其生理作用尚不清楚。本文报道了野生型人Cgb铁态的X射线晶体结构，分辨率为2.4 μ m。在晶体结构中，铁Cgb通过Cys 38（B2）和Cys 83（E9）之间的两个分子间二硫键二聚，二聚界面类似于七鳃鳗Hb和Ngb。Cgb单体的整体骨架结构表现出传统的珠蛋白折叠，具有三对三的α-螺旋三明治结构，其中螺旋的排列在迄今为止研究的所有珠蛋白中基本相同。一个详细的比较表明，D螺旋区的CD角的骨干结构，N端的E-螺旋和F-螺旋的CGB类似更密切的五配位球蛋白（Mb，七鳃鳗血红蛋白），而不是hexacoordinated球蛋白（Ngb，水稻血红蛋白）。然而，His 81（E7）咪唑基团直接与血红素铁配位，作为第六轴配体，形成六配位血红素，如Ngb和水稻Hb。血红素口袋中高度保守的残基（Phe（CD 1）、瓦尔（E11）、远端His（E7）和近端His（F8））的位置和方向与其他珠蛋白的那些相似。观察到Arg 84（E10）胍基团的两种替代构象，表明它参与了与Cgb的配体结合，就像Astrasia Mb的Arg（E10）和Ngb的Lys（E10）一样。球蛋白质之间的结构差异和相似性与分子进化关系进行了讨论。
Cytoglobin (Cgb), a newly discovered member of the vertebrate globin family, binds O2reversibly via its heme, as is the case for other mammalian globins (hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb)). While Cgb is expressed in various tissues, its physiological role is not clearly understood. Here, the X-ray crystal structure of wild type human Cgb in the ferric state at 2.4Å resolution is reported. In the crystal structure, ferric Cgb is dimerized through two intermolecular disulfide bonds between Cys38(B2) and Cys83(E9), and the dimerization interface is similar to that of lamprey Hb and Ngb. The overall backbone structure of the Cgb monomer exhibits a traditional globin fold with a three-over-three α-helical sandwich, in which the arrangement of helices is basically the same among all globins studied to date. A detailed comparison reveals that the backbone structure of the CD corner to D helix region, the N terminus of the E-helix and the F-helix of Cgb resembles more closely those of pentacoordinated globins (Mb, lamprey Hb), rather than hexacoordinated globins (Ngb, rice Hb). However, the His81(E7) imidazole group coordinates directly to the heme iron as a sixth axial ligand to form a hexcoordinated heme, like Ngb and rice Hb. The position and orientation of the highly conserved residues in the heme pocket (Phe(CD1), Val(E11), distal His(E7) and proximal His(F8)) are similar to those of other globin proteins. Two alternative conformations of the Arg84(E10) guanidium group were observed, suggesting that it participates in ligand binding to Cgb, as is the case for Arg(E10) of Aplysia Mb and Lys(E10) of Ngb. The structural diversities and similarities among globin proteins are discussed with relevance to molecular evolutionary relationships.