Protein Subunit-Subunit to Domain-Domain Interactions
01 Jan 2018-pp 133-142
TL;DR: This work describes this phenomenon using illustrations of chimeric protein sequences in comparison with known structures for both fused and unfused forms, and describes the possible mechanism with appropriate hypothesis using available structural complexes of some known examples.
Abstract: Fusion proteins often referred to as “rosetta stone” occur through an important evolutionary phenomenon called gene fusion. This results in chimeric sequences in one species compared to its unfused individual component sequences in yet another species. Thus, a functional “subunit-subunit” interface in one species has evolved to form a functional “domain-domain” interface in yet another species. Therefore, it is important to describe such events and its possible mechanism with appropriate hypothesis using available structural complexes of some known examples. We describe this phenomenon using illustrations of chimeric protein sequences in comparison with known structures for both fused and unfused forms.
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TL;DR: This report focuses on identifying, analyzing, and tabulating human fusion proteins of prokaryotic origin found to mimic operons, simulate protein-protein interfaces in proKaryotes, exhibiting multiple functions and alternative splicing in humans.
Abstract: Gene fusion has been described as an important evolutionary phenomenon. This report focuses on identifying, analyzing, and tabulating human fusion proteins of prokaryotic origin. These fusion proteins are found to mimic operons, simulate protein-protein interfaces in prokaryotes, exhibiting multiple functions and alternative splicing in humans. The accredited biological functions for each of these proteins is made available as a database at http://sege.ntu.edu.sg/wester/fusion/
10 citations
TL;DR: The association of six fusion proteins with the citric acid cycle and their capability to produce metabolites with high connectivity index suggests that fusion gene products and their evolution have had a key role in the selection of complex multifaceted networks.
Abstract: Human fusion proteins consisting of two or more fusion partners of prokaryotic origin exhibit accreted function. Recent studies have elucidated the importance of fusion proteins in complex regulatory networks. The significance of fusion proteins in cellular networks and their evolutionary mechanism is largely unknown. Here, we discuss the association of six fusion proteins with the citric acid cycle. We define possible gene fusion scenarios and show that they produce metabolites with high connectivity for complex networking. Complex networking of metabolites requires proteins with incremental structural architectures and functional capabilities. Such higher order functionality is frequently provided by fusion proteins. Therefore, evolution of fusion proteins capable of producing metabolites with greater connectivity for enhanced cross-talk between pathways is critical for the selection of multiple trajectories in maintaining a stoichiometric balance during regulation. The association of six fusion proteins with the citric acid cycle and their capability to produce metabolites with high connectivity index is intriguing. This suggests that fusion gene products and their evolution have had a key role in the selection of complex multifaceted networks. In addition, we propose that fusion proteins have gained additive biochemical function for a balanced regulation of metabolic networks.
7 citations
TL;DR: Structural features for the first time demonstrate the evolutionary advantage in generating proteins with novel structural architecture through gene fusion by showing that fused IGPS in SC has larger interface area between HisFHisH and greater radius of gyration compared to un-fusedIGPS in TT.
Abstract: Gene fusion produces proteins with novel structural architectures during evolution. Recent comparative genome analysis shows several cases of fusion/fission across distant phylogeny. However, the selection forces driving gene fusion are not fully understood due to the lack of structural, dynamics and kinetics data. Available structural data at PDB (protein databank) contains limited cases of structural pairs describing fused and un-fused structures. Nonetheless, we identified a pair of IGPS (imidazole glycerol phosphate synthetase) structures (comprising of HisF - glutaminase unit and HisH - cyclase unit) from S. cerevisiae (SC) and T. thermophilus (TT). The HisF-HisH structural units are domains in SC and subunits in TT. Hence, they are fused in SC and un-fused in TT. Subsequently, a domain-domain interface is formed in SC and a subunit-subunit interface in TT between HisF and HisH. Our interest is to document the structure and dynamics differences between fused and un-fused IGPS. Therefore, we probed into the structures of fused IGPS in SC and un-fused IGPS in TT using molecular dynamics simulation for 5ns. Simulation shows that fused IGPS in SC has larger interface area between HisF-HisH and greater radius of gyration compared to un-fused IGPS in TT. These structural features for the first time demonstrate the evolutionary advantage in generating proteins with novel structural architecture through gene fusion.
7 citations