Liu Y, Hart P J, Schlunegger M P, Eisenberg D
University of California-Department of Energy Laboratory of Structural Biology and Molecular Medicine, Departments of Chemistry and Biochemistry and Biological Chemistry, University of California, Los Angeles, CA 90095-1570, USA.
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3437-42. doi: 10.1073/pnas.95.7.3437.
The dimer of bovine pancreatic ribonuclease A (RNase A) discovered by Crestfield, Stein, and Moore in 1962 has been crystallized and its structure determined and refined to a 2.1-A resolution. The dimer is 3D domain-swapped. The N-terminal helix (residues 1-15) of each subunit is swapped into the major domain (residues 23-124) of the other subunit. The dimer of bull seminal ribonuclease (BS-RNase) is also known to be domain-swapped, but the relationship of the subunits within the two dimers is strikingly different. In the RNase A dimer, the 3-stranded beta sheets of the two subunits are hydrogen-bonded at their edges to form a continuous 6-stranded sheet across the dimer interface; in the BS-RNase dimer, it is instead the two helices that abut. Whereas the BS-RNase dimer has 2-fold molecular symmetry, the two subunits of the RNase A dimer are related by a rotation of approximately 160 degrees. Taken together, these structures show that intersubunit adhesion comes mainly from the swapped helical domain binding to the other subunit in the "closed interface" but that the overall architecture of the domain-swapped oligomer depends on the interactions in the second type of interface, the "open interface." The RNase A dimer crystals take up the dye Congo Red, but the structure of a Congo Red-stained crystal reveals no bound dye molecule. Dimer formation is inhibited by excess amounts of the swapped helical domain. The possible implications for amyloid formation are discussed.
1962年，克雷斯特菲尔德、斯坦因和摩尔发现的牛胰核糖核酸酶A（RNase A）二聚体已被结晶，其结构已确定并精修至2.1埃分辨率。该二聚体是三维结构域交换的。每个亚基的N端螺旋（残基1 - 15）交换到另一个亚基的主要结构域（残基23 - 124）中。已知公牛精液核糖核酸酶（BS - RNase）的二聚体也是结构域交换的，但两个二聚体中亚基之间的关系显著不同。在RNase A二聚体中，两个亚基的三链β折叠在其边缘通过氢键结合，在二聚体界面形成一个连续的六链折叠；而在BS - RNase二聚体中，取而代之的是两个螺旋相邻。虽然BS - RNase二聚体具有二重分子对称性，但RNase A二聚体的两个亚基通过大约160度的旋转相关联。综上所述，这些结构表明亚基间的黏附主要来自于在“封闭界面”中交换的螺旋结构域与另一个亚基的结合，但结构域交换寡聚体的整体结构取决于第二种界面即“开放界面”中的相互作用。RNase A二聚体晶体能够吸收染料刚果红，但刚果红染色晶体的结构显示没有结合的染料分子。过量的交换螺旋结构域会抑制二聚体的形成。文中还讨论了其对淀粉样蛋白形成的可能影响。
