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Analysis of Protectin: From Structure to Function in Biology

Explore the genomic location, primary and tertiary structure, function, and deficiencies of Protectin protein implicated in immune defense and transplantation. Understand its role in preventing membrane attack complex and implications in human diseases. Discover its structural similarities with snake venom neurotoxins and its evolution.

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Analysis of Protectin: From Structure to Function in Biology

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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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