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Analysis of Protectin
Jeff MesserGuillermo Vargas
Andres Murillo
Like Most Things in Biology, Protectin Is Known by Several Names.
• 1F-5Ag
• H19
• HRF20
• MACIF
• MIRL
• P-18
• CD59
The Basics at the DNA Level
• Genomic location: 33845931 - 33859721 bp (33.8 Mb) on chromosome 11p13
• Total length: 1858 bp • Number of Exons: 3
• View chromosome• View exons
Primary Structure• Sequence length: 128 amino acids
• Functional part: 27 - 70
TMAP Output
Family Matters• Protectin is a member of the Ly-6 superfamily
which are cell-surface molecules. Surprisingly, they both also share a very similar structure with snake venom neurotoxins.
Finally…Protectin’s Function
• This is a widely distributed protein that inhibits the membrane attack complex (MAC).
• In other words, it protects cells from the immune system.
Membrane Attack Complex
Function
CD59 Deficiency
• (1992) single nucleotide deletions in codon 16 (GCC to GC) and codon 96 (GCA to CA). Deletion in codon 16 resulted in a frameshift and introduced a stop codon at position 54
• Hemolytic Anemia and Thrombosis
• Causing Cerebral Infarction
More CD59 Deficiencies
• Paroxysmal Nocturnal Nemoglobinuria (Rosse, 1993), which is a disorder ofPIGA
• Intravascular Hemolysis
• Resulting in Anemia and later Leukemia
Why Should I Care?
• Protectin may prolong the survival of animal organs in human transplantation.
Tertiary Structure
• The tertiary structure was extrapolated through 2D NMR.
• Relatively flat, disk shaped.
• Main structure:– 2 anti-parallel beta-sheets in one “finger.”– 3 anti-parallel beta-sheets form the core.
• 5 disulfide-bonded cysteine pairs.
3D Structures on the Web
• CD59 – Human Complement Regulatory Protein, PDB ID: 1ERG
• SCOP: Protein: CD59 from Homo sapiens
• SCOP: Protein: Erabutoxin B (also neurotoxin B) from Sea snake (Laticauda semifasciata)
Protein/Structural Evolution• Similar structure of snake venom
neurotoxins
Links to the Past
Similarities in Herpes Virus
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