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Analysis of Protectin Jeff Messer Guillermo Vargas Andres Murillo

Analysis of Protectin Jeff Messer Guillermo 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

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Analysis of Protectin Jeff Messer Guillermo Vargas Andres Murillo

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  1. Analysis of ProtectinJeff MesserGuillermo VargasAndres Murillo

  2. Like Most Things in Biology, Protectin Is Known by Several Names. • 1F-5Ag • H19 • HRF20 • MACIF • MIRL • P-18 • CD59

  3. 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

  4. Primary Structure • Sequence length: 128 amino acids • Functional part: 27 - 70

  5. TMAP Output

  6. 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.

  7. 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.

  8. Membrane Attack Complex

  9. Function

  10. 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

  11. More CD59 Deficiencies • Paroxysmal Nocturnal Nemoglobinuria (Rosse, 1993), which is a disorder ofPIGA • Intravascular Hemolysis • Resulting in Anemia and later Leukemia

  12. Why Should I Care? • Protectin may prolong the survival of animal organs in human transplantation.

  13. 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.

  14. 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)

  15. Protein/Structural Evolution • Similar structure of snake venom neurotoxins

  16. Links to the Past

  17. Similarities in Herpes Virus

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