STRUCTURE OF HUMAN PLASMA PREALBUMIN AT 2.5 A RESOLUTION - PRELIMINARY REPORT ON POLYPEPTIDE-CHAIN CONFORMATION, QUATERNARY STRUCTURE AND THYROXINE BINDING
STRUCTURE OF HUMAN PLASMA PREALBUMIN AT 2.5 A RESOLUTION - PRELIMINARY REPORT ON POLYPEPTIDE-CHAIN CONFORMATION, QUATERNARY STRUCTURE AND THYROXINE BINDING
复制标题
DOI：
10.1016/0022-2836(74)90291-5
复制
发表时间：
1974-01-01
影响因子：
5.6
通讯作者：
SWAN, IDA
中科院分区：
文献类型：
--
作者：
BLAKE, CCF;GEISOW, MJ;SWAN, IDA
用三种同晶衍生物计算了人血浆前白蛋白的2.5 μ m分辨电子密度图。对图谱的解释表明，该分子是由相同的亚基组成的四聚体。每个亚基由含有124至128个残基的单个多肽链组成，这与54，000的四聚体分子量一致。每个单体中的一半残基被组织成两个广泛的β-折叠，每个β-折叠由四条链组成。所有的链相互作用都是反平行的，只有一个例外。剩下的残基参与各种环，将β链连接在一起，其中一个环含有非常短的α螺旋。单体的形状为长椭圆体，两个β-折叠形成了其表面的很大一部分。单体通过进一步的反平行β-折叠相互作用连接成稳定的二聚体，其中每个单体的β-折叠边缘都有等效链。这使得二聚体有两个β折叠，每个β折叠由八条链组成，其中四条来自一个单体，四条来自另一个单体。二聚体组装成完整的四聚体分子，其中来自每个二聚体的等效β-折叠在分子的中心相对。这些β-折叠通过形成主要二聚体-二聚体相互作用的每个单体的短链环保持在大于接触距离的位置。相对但分离的β-折叠形成了一个贯穿分子中心的大槽的表面。甲状腺素和三碘甲状腺原氨酸与前白蛋白结合的低分辨率X射线分析表明，激素结合在两个与甲状腺相关的结合位点，位于中央槽的深处。
A 2.5 Å resolution electron density map of human plasma prealbumin has been calculated using three isomorphous derivatives. Interpretation of the map shows that the molecule is a tetramer composed of identical subunits. Each subunit is composed of a single polypeptide chain containing between 124 and 128 residues, which is consistent with the tetramer molecular weight of 54,000. Half the residues in each monomer are organized into two extensive β-sheets each composed of four strands. All the strand interactions are antiparallel, with one exception. The remaining residues are involved in loops of various kinds that link the β-strands together, one of which contains a very short α-helix. The isolated monomer has the shape of a prolate ellipsoid, with the two β-sheets forming a large part of its surface.The monomers are linked into stable dimers by further antiparallel β-sheet interactions involving equivalent strands at the edge of each of the monomer's β-sheets. This gives the dimer two β-sheets each composed of eight strands, four of which derive from one monomer and four from the other. The dimers are assembled into the complete tetrameric molecule with equivalent β-sheets from each dimer opposed at the centre of the molecule. These β-sheets are kept at greater than contact distance by a short loop of chain from each monomer that forms the major dimer-dimer interaction. The opposed, but separated, β-sheets, form the surface of a large slot that runs through the centre of the molecule. Low-resolution X-ray analysis of the binding of thyroxine and tri-iodothyronine to prealbumin shows that the hormones are bound in two symmetry-related binding sites located deeply in the central slot.