Protein salvage and repurposing in evolution: Phospholipase D toxins are stabilized by a remodeled scrap of a membrane association domain
Protein salvage and repurposing in evolution: Phospholipase D toxins are stabilized by a remodeled scrap of a membrane association domain
复制标题
DOI：
10.1002/pro.4701
复制
发表时间：
2023-07-01
期刊：
影响因子：
8
通讯作者：
Binford，Greta J.
中科院分区：
文献类型：
--
作者：
Cordes，Matthew H. J.;Sundman，Alexandra K.;Binford，Greta J.
甘油磷酸二酯磷酸二酯酶（GDPD）样SMaseD/PLD结构域家族，包括隐居蜘蛛和放线菌中的磷脂酶D（PLD）毒素，在细菌中从GDPD进化而来。PLD酶保留了GDPD的核心（β/α）8桶折叠，同时获得了标志性的C末端扩展基序并失去了一个小的插入结构域。使用序列比对和系统发育分析，我们推断C-末端基序来自一个古老的细菌PLAT结构域的片段。形式上，含有PLAT结构域重复序列的蛋白质的一部分与GDPD桶的C末端融合，导致PLAT结构域的一个区段的连接，随后是第二个完整的PLAT结构域。完整的结构域只保留在一些基本的同源物，但PLAT节段是保守的，并作为扩展基序重新利用。PLAT片段对应于β-夹心的β7-β8链，而蜘蛛PLD毒素中代表的扩展基序已被重塑为α-螺旋、β-链和有序环。GDPD-PLAT融合导致在建立GDPD样SMaseD/PLD家族中的两个收购：（1）可能通过介导膜缔合支持早期脂肪酶活性的PLAT结构域，以及（2）puronectin稳定催化结构域的扩展基序，可能补偿或允许插入结构域的丢失。更重要的是，混乱的域洗牌事件可能会留下一些域碎片，这些碎片可以被抢救、改造和重新利用。
The glycerophosphodiester phosphodiesterase (GDPD)‐like SMaseD/PLD domain family, which includes phospholipase D (PLD) toxins in recluse spiders and actinobacteria, evolved anciently in bacteria from the GDPD. The PLD enzymes retained the core (β/α)8barrel fold of GDPD, while gaining a signature C‐terminal expansion motif and losing a small insertion domain. Using sequence alignments and phylogenetic analysis, we infer that the C‐terminal motif derives from a segment of an ancient bacterial PLAT domain. Formally, part of a protein containing a PLAT domain repeat underwent fusion to the C terminus of a GDPD barrel, leading to attachment of a segment of a PLAT domain, followed by a second complete PLAT domain. The complete domain was retained only in some basal homologs, but the PLAT segment was conserved and repurposed as the expansion motif. The PLAT segment corresponds to strands β7–β8 of a β‐sandwich, while the expansion motif as represented in spider PLD toxins has been remodeled as an α‐helix, a β‐strand, and an ordered loop. The GDPD‐PLAT fusion led to two acquisitions in founding the GDPD‐like SMaseD/PLD family: (1) a PLAT domain that presumably supported early lipase activity by mediating membrane association, and (2) an expansion motif that putatively stabilized the catalytic domain, possibly compensating for, or permitting, loss of the insertion domain. Of wider significance, messy domain shuffling events can leave behind scraps of domains that can be salvaged, remodeled, and repurposed.