PAN
domains have significant functional versatility fulfilling diverse
biological
Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, origin, evolution, and distribution of ...
roles by mediating
protein-protein and
protein-carbohydrate interactions.
These domains contain a
hair-pin loop like structure, similar to that found in
knottins but with a different pattern of
disulfide bond
In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups.
In inor ...
s.
It has been shown that the N-terminal domains of members of the
plasminogen
Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is enco ...
/
hepatocyte growth factor
Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts ...
family, the apple domains of the
plasma prekallikrein
Prekallikrein (PK), also known as Fletcher factor, is an 85,000 Mr serine protease that complexes with high-molecular-weight kininogen. PK is the precursor of plasma kallikrein, which is a serine protease that activates kinins. PK is cleaved to ...
/
coagulation factor XI family, and domains of various
nematode
The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...
proteins belong to the same module superfamily, the PAN module.
The PAN domain contains a
conserved core of three disulfide bridges. In some members of the family there is an additional fourth disulfide bridge that links the
N- and
C-termini
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When ...
of the domain.
The apple domain, as well as other examples of the PAN domain, consists of seven
β-strand
The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...
s that fold into a curved antiparallel
sheet cradling an
α-helix
An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix).
The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...
. Two disulfide bonds lock the helix onto the central β4 and β5 strands, whereas a third connects the N- and C-termini of the domain. In the apple domain, the β4–β5 loop and β5–β6 crossover loop generate a small pocket on the opposite side of the sheet from the α-helix.
In native plasminogen the PAN domain is associated with five
kringle
Kringle (, ) is a Northern European pastry, a variety of pretzel. Pretzels were introduced by Roman Catholic monks in the 13th century in Denmark, and from there they spread throughout Scandinavia and evolved into several kinds of sweet, salty o ...
domains.
The interactions between the PAN domain and the kringles play a critical role in stabilising the quaternary complex of the native plasminogen;
References
Protein domains
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