Bacterial Pleckstrin Homology Domains: A Prokaryotic Origin for the PH Domain |
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Institution: | 1 Joint Center for Structural Genomics, http://www.jcsg.org 2 Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA 3 The Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK 4 Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA 5 Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA 92093, USA 6 Program on Bioinformatics and Systems Biology, Burnham Institute for Medical Research, La Jolla, CA 92037, USA 7 Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA 8 Photon Science, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA |
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Abstract: | Pleckstrin homology (PH) domains have been identified only in eukaryotic proteins to date. We have determined crystal structures for three members of an uncharacterized protein family (Pfam PF08000), which provide compelling evidence for the existence of PH-like domains in bacteria (PHb). The first two structures contain a single PHb domain that forms a dome-shaped, oligomeric ring with C5 symmetry. The third structure has an additional helical hairpin attached at the C-terminus and forms a similar but much larger ring with C12 symmetry. Thus, both molecular assemblies exhibit rare, higher-order, cyclic symmetry but preserve a similar arrangement of their PHb domains, which gives rise to a conserved hydrophilic surface at the intersection of the β-strands of adjacent protomers that likely mediates protein-protein interactions. As a result of these structures, additional families of PHb domains were identified, suggesting that PH domains are much more widespread than originally anticipated. Thus, rather than being a eukaryotic innovation, the PH domain superfamily appears to have existed before prokaryotes and eukaryotes diverged. |
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Keywords: | PH Pleckstrin homology PHb bacterial PH domain PTB phosphotyrosine binding VPS36 vacuolar protein sorting protein 36 DUF1696 domain of unknown function family 1696 JCSG Joint Center for Structural Genomics MAD multiwavelength anomalous diffraction PEG polyethylene glycol asu asymmetric unit PDB Protein Data Bank PIPE Polymerase Incomplete Primer Extension TEV tobacco etch virus TCEP tris(2-carboxyethyl)phosphine-HCl SSRL Stanford Synchrotron Radiation Lightsource ALS Advanced Light Source |
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