Callebaut I, Portetelle D, Burny A, Mornon J P
Département des Macromolécules Biologiques--Laboratoire de Minéralogie-Cristallographie, CNRS URA09, Universités Paris, France.
Eur J Biochem. 1994 Jun 1;222(2):405-14. doi: 10.1111/j.1432-1033.1994.tb18879.x.
Sequence analysis using the sensitive hydrophobic cluster analysis method shows that the bovine leukemia virus envelope glycoproteins conserve the general organization of the influenza hemagglutinin into a 'stem', containing the external part of the transmembrane glycoprotein and the N-terminal and C-terminal parts of the external glycoprotein, and a 'head', containing only external glycoprotein residues. However, our analysis suggests, for the first time, that the bovine leukemia virus envelope head will not adopt the typical 'jelly-roll' fold of the influenza A hemagglutinin head, but most likely folds into another type of 'Greek-key' structure corresponding to the overall topology of constant immunoglobulin domains. We constructed a three-dimensional model for the bovine leukemia virus envelope head by homology modeling using the crystal structure of the human histocompatibility antigen HLA-A2 alpha 3 domain. Furthermore, we propose a general model for the oligomeric organization of this head, based on the hemagglutinin trimer. The proposed structural organization of bovine leukemia virus external glycoprotein is further supported by antipeptide and monoclonal antibody reactivities. Our modeling study suggests that the loops of the two neutralizing peptides located in the head are adjacent at the top of the domain and define a potential interaction site of the external glycoprotein with its cellular receptor. This site is topologically similar to the binding site of hemagglutinin with its cellular receptor, sialic acid. The other neutralizing peptides are located within a small domain linking the head to the stem. These data are of interest for defining other oncoviral glycoproteins heads and receptor-binding sites.
使用灵敏的疏水簇分析方法进行的序列分析表明，牛白血病病毒包膜糖蛋白保留了流感血凝素的总体结构，即一个“柄部”，包含跨膜糖蛋白的外部部分以及外部糖蛋白的N端和C端部分，和一个“头部”，仅包含外部糖蛋白残基。然而，我们的分析首次表明，牛白血病病毒包膜头部不会采用甲型流感血凝素头部典型的“果冻卷”折叠方式，而是很可能折叠成另一种对应于恒定免疫球蛋白结构域整体拓扑结构的“希腊钥匙”结构。我们利用人类组织相容性抗原HLA - A2α3结构域的晶体结构，通过同源建模构建了牛白血病病毒包膜头部的三维模型。此外，基于血凝素三聚体，我们提出了该头部寡聚组织的通用模型。抗肽和单克隆抗体反应性进一步支持了所提出的牛白血病病毒外部糖蛋白的结构组织。我们的建模研究表明，位于头部的两种中和肽的环在结构域顶部相邻，并定义了外部糖蛋白与其细胞受体的潜在相互作用位点。该位点在拓扑结构上类似于血凝素与其细胞受体唾液酸的结合位点。其他中和肽位于连接头部和柄部的一个小结构域内。这些数据对于定义其他肿瘤病毒糖蛋白头部和受体结合位点具有重要意义。
