Analysis of Protectin - Cognitive Studies at CSU Stanislaus

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Transcript Analysis of Protectin - Cognitive Studies at CSU Stanislaus

Analysis of Protectin
Jeff Messer
Guillermo Vargas
Andres Murillo
Like Most Things in Biology, Protectin
Is Known by Several Names.
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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 of
PIGA
• 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