Assembly reflects evolution of protein complexes. Export

@article{levy_08_assembly, abstract = {A homomer is formed by self-interacting copies of a protein unit. This is functionally important, as in allostery, and structurally crucial because mis-assembly of homomers is implicated in disease. Homomers are widespread, with 50-70\% of proteins with a known quaternary state assembling into such structures. Despite their prevalence, their role in the evolution of cellular machinery and the potential for their use in the design of new molecular machines, little is known about the mechanisms that drive formation of homomers at the level of evolution and assembly in the cell. Here we present an analysis of over 5,000 unique atomic structures and show that the quaternary structure of homomers is conserved in over 70\% of protein pairs sharing as little as 30\% sequence identity. Where quaternary structure is not conserved among the members of a protein family, a detailed investigation revealed well-defined evolutionary pathways by which proteins transit between different quaternary structure types. Furthermore, we show by perturbing subunit interfaces within complexes and by mass spectrometry analysis, that the (dis)assembly pathway mimics the evolutionary pathway. These data represent a molecular analogy to Haeckel's evolutionary paradigm of embryonic development, where an intermediate in the assembly of a complex represents a form that appeared in its own evolutionary history. Our model of self-assembly allows reliable prediction of evolution and assembly of a complex solely from its crystal structure.}, author = {Levy, Emmanuel D. and Erba, Elisabetta B. and Robinson, Carol V. and Teichmann, Sarah A.}, citeulike-article-id = {2908168}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature06942}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature06942}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18563089}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18563089}, citeulike-linkout-4 = {http://dx.doi.org/http://dx.doi.org/10.1038/nature06942}, citeulike-linkout-5 = {http://dx.doi.org/10.1038/nature06942}, comment = {"This is the first time that a general principle for formation and assembly of homomers has been demonstrated."}, day = {26}, doi = {10.1038/nature06942}, issn = {1476-4687}, journal = {Nature}, keywords = {complexes, evolution, experimental, ppi, proj\_assembly, structure}, month = {June}, number = {7199}, pages = {1262--1265}, posted-at = {2008-10-14 14:51:52}, priority = {0}, publisher = {Nature Publishing Group}, title = {Assembly reflects evolution of protein complexes.}, url = {http://dx.doi.org/10.1038/nature06942}, volume = {453}, year = {2008} }

TY - JOUR ID - levy_08_assembly L3 - citeulike-article-id:2908168 N2 - A homomer is formed by self-interacting copies of a protein unit. This is functionally important, as in allostery, and structurally crucial because mis-assembly of homomers is implicated in disease. Homomers are widespread, with 50-70% of proteins with a known quaternary state assembling into such structures. Despite their prevalence, their role in the evolution of cellular machinery and the potential for their use in the design of new molecular machines, little is known about the mechanisms that drive formation of homomers at the level of evolution and assembly in the cell. Here we present an analysis of over 5,000 unique atomic structures and show that the quaternary structure of homomers is conserved in over 70% of protein pairs sharing as little as 30% sequence identity. Where quaternary structure is not conserved among the members of a protein family, a detailed investigation revealed well-defined evolutionary pathways by which proteins transit between different quaternary structure types. Furthermore, we show by perturbing subunit interfaces within complexes and by mass spectrometry analysis, that the (dis)assembly pathway mimics the evolutionary pathway. These data represent a molecular analogy to Haeckel's evolutionary paradigm of embryonic development, where an intermediate in the assembly of a complex represents a form that appeared in its own evolutionary history. Our model of self-assembly allows reliable prediction of evolution and assembly of a complex solely from its crystal structure. IS - 7199 JF - Nature SN - 1476-4687 EP - 1265 TI - Assembly reflects evolution of protein complexes. PB - Nature Publishing Group VL - 453 SP - 1262 KW - complexes KW - evolution KW - experimental KW - ppi KW - proj_assembly KW - structure N1 - "This is the first time that a general principle for formation and assembly of homomers has been demonstrated." AU - Levy, Emmanuel AU - Erba, Elisabetta AU - Robinson, Carol AU - Teichmann, Sarah PY - 2008/June/26/ UR - http://dx.doi.org/10.1038/nature06942 ER -