1cdr
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STRUCTURE OF A SOLUBLE, GLYCOSYLATED FORM OF THE HUMAN COMPLEMENT REGULATORY PROTEIN CD59
OverviewOverview
BACKGROUND: CD59 is a cell-surface glycoprotein that protects host cells from complement-mediated lysis by binding to and preventing the normal functioning of the complement proteins C8 and/or C9 which form part of a membrane penetrating assembly called the membrane attack complex. CD59 has no structural similarity to other complement proteins, but is an example of a plasma protein domain type found also in murine Ly-6 proteins and the urokinase-type plasminogen activator receptor. RESULTS: CD59 was purified from human urine, retaining the N-glycan and at least some of the non-lipid component of the glycosylphosphatidylinositol membrane anchor. The three-dimensional structure of the protein component has been determined in the presence of the carbohydrate groups using two-dimensional NMR spectroscopy. The protein structure is well defined by the NMR data (root mean square deviation from the mean structure of 0.65 A for backbone atoms and no distance constraint violations greater than 0.4 A). Structure calculations were also carried out to model the orientation of the N-acetylglucosamine residue that is directly linked to Asn18. CONCLUSIONS: The main features of the protein structure are two antiparallel beta-sheets (a central one with three strands and another with two), a short helix that packs against the three-stranded beta-sheet, and a carboxy-terminal region that, although lacking regular secondary structure, is well defined and packs against the three-stranded beta-sheet, on the opposite face to the helix. We have used the structure, in combination with existing biochemical data, to identify residues that may be involved in C8 binding.
DiseaseDisease
Known disease associated with this structure: CD59 deficiency OMIM:[107271]
About this StructureAbout this Structure
1CDR is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Structure of a soluble, glycosylated form of the human complement regulatory protein CD59., Fletcher CM, Harrison RA, Lachmann PJ, Neuhaus D, Structure. 1994 Mar 15;2(3):185-99. PMID:7520819
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