analysis of protectin jeff messer guillermo vargas andres murillo

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