Abstract
DING proteins constitute an intriguing family of phosphate-binding proteins that was identified in a wide range of organisms, from prokaryotes and archae to eukaryotes. Despite their seemingly ubiquitous occurrence in eukaryotes, their encoding genes are missing from sequenced genomes. Such a lack has considerably hampered functional studies. In humans, these proteins have been related to several diseases, like atherosclerosis, kidney stones, inflammation processes and HIV inhibition. The human phosphate binding protein is a human representative of the DING family that was serendipitously discovered from human plasma. An original approach was developed to determine ab initio the complete and exact sequence of this 38 kDa protein by utilizing mass spectrometry and X-ray data in tandem. Taking advantage of this first complete eukaryotic DING sequence, a immunohistochemistry study was undertaken to check the presence of DING proteins in various mice tissues, revealing that these proteins are widely expressed. Finally, the structure of a bacterial representative from Pseudomonas fluorescens was solved at sub-angstrom resolution, allowing the molecular mechanism of the phosphate binding in these high-affinity proteins to be elucidated.
Highlights
DING proteins constitute an intriguing family of phosphatebinding proteins named DING according to their four conserved N-terminal residues (Berna et al, 2002)
The primary sequence obtained by X-ray crystallography was used like an ‘Ariane wire’, useful to align peptide sequences subsequently obtained by mass spectrometry, without the need of having overlapping peptides
The DING proteins family is an intriguing protein family that seems ubiquitous in eukaryotes, albeit their coding genes are missing
Summary
DING proteins constitute an intriguing family of phosphatebinding proteins named DING according to their four conserved N-terminal residues (Berna et al, 2002). 18, 45–49 sequence identity between the known DING representatives is about 90% at the nucleotidic level, over more than 600 base pairs (Morales et al, 2006) This high conservation raised controversy about their prokaryotic (Lewis & Crowther, 2005) or eukaryotic origins (Berna, Scott et al, 2009). Several DING proteins have been identified from different tissues, including the crystal adhesion inhibitor (CAI), the human synovial stimulatory protein (SSP), X-DING-CD4+ from human CD4+ T lymphocytes and the human phosphate binding protein (HPBP). Comparison of available peptides sequences of HPBP, CAI, SSP and X-DING-CD4+ strongly suggests that these proteins are encoded by four different genes, all lacking the sequenced human genome. The involvement of DING proteins in a large spectrum of diseases enhances the potential therapeutic value of this specific protein family, but the lack of sequences has considerably hampered the functional studies within this protein family
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
