Radauer Christian, Lackner Peter, Breiteneder Heimo
Department of Pathophysiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
BMC Evol Biol. 2008 Oct 15;8:286. doi: 10.1186/1471-2148-8-286.
The major birch pollen allergen, Bet v 1, is a member of the ubiquitous PR-10 family of plant pathogenesis-related proteins. In recent years, a number of diverse plant proteins with low sequence similarity to Bet v 1 was identified. In addition, determination of the Bet v 1 structure revealed the existence of a large superfamily of structurally related proteins. In this study, we aimed to identify and classify all Bet v 1-related structures from the Protein Data Bank and all Bet v 1-related sequences from the Uniprot database.
Structural comparisons of representative members of already known protein families structurally related to Bet v 1 with all entries of the Protein Data Bank yielded 47 structures with non-identical sequences. They were classified into eleven families, five of which were newly identified and not included in the Structural Classification of Proteins database release 1.71. The taxonomic distribution of these families extracted from the Pfam protein family database showed that members of the polyketide cyclase family and the activator of Hsp90 ATPase homologue 1 family were distributed among all three superkingdoms, while members of some bacterial families were confined to a small number of species. Comparison of ligand binding activities of Bet v 1-like superfamily members revealed that their functions were related to binding and metabolism of large, hydrophobic compounds such as lipids, hormones, and antibiotics. Phylogenetic relationships within the Bet v 1 family, defined as the group of proteins with significant sequence similarity to Bet v 1, were determined by aligning 264 Bet v 1-related sequences. A distance-based phylogenetic tree yielded a classification into 11 subfamilies, nine exclusively containing plant sequences and two subfamilies of bacterial proteins. Plant sequences included the pathogenesis-related proteins 10, the major latex proteins/ripening-related proteins subfamily, and polyketide cyclase-like sequences.
The ubiquitous distribution of Bet v 1-related proteins among all superkingdoms suggests that a Bet v 1-like protein was already present in the last universal common ancestor. During evolution, this protein diversified into numerous families with low sequence similarity but with a common fold that succeeded as a versatile scaffold for binding of bulky ligands.
主要的桦树花粉过敏原Bet v 1是植物病程相关蛋白中普遍存在的PR - 10家族的成员。近年来，已鉴定出许多与Bet v 1序列相似性较低的不同植物蛋白。此外，Bet v 1结构的测定揭示了一个结构相关蛋白的大型超家族的存在。在本研究中，我们旨在从蛋白质数据库（Protein Data Bank）中鉴定并分类所有与Bet v 1相关的结构，以及从通用蛋白质数据库（Uniprot database）中鉴定并分类所有与Bet v 1相关的序列。
将与Bet v 1结构相关的已知蛋白质家族的代表性成员与蛋白质数据库的所有条目进行结构比较，得到了47个序列不同的结构。它们被分为11个家族，其中5个是新鉴定的，未包含在蛋白质结构分类数据库1.71版本中。从Pfam蛋白质家族数据库中提取的这些家族的分类分布表明，聚酮环化酶家族和热休克蛋白90 ATP酶同源物1激活剂家族的成员分布在所有三个超界中，而一些细菌家族的成员则局限于少数物种。对Bet v 1样超家族成员的配体结合活性进行比较，发现它们的功能与脂质、激素和抗生素等大型疏水性化合物的结合和代谢有关。通过比对264个与Bet v 1相关的序列，确定了Bet v 1家族（定义为与Bet v 1具有显著序列相似性的蛋白质组）内的系统发育关系。基于距离的系统发育树将其分为11个亚家族，其中9个亚家族仅包含植物序列，2个亚家族为细菌蛋白。植物序列包括病程相关蛋白10、主要乳胶蛋白/成熟相关蛋白亚家族和聚酮环化酶样序列。
Bet v 1相关蛋白在所有超界中的广泛分布表明，一种类似Bet v 1的蛋白在最后的共同祖先中就已存在。在进化过程中，这种蛋白分化为众多序列相似性较低但具有共同折叠结构的家族，该结构成功地成为了结合大分子配体的通用支架。
