{PDOC51865}
{PS51865; PDZ_GRASP}
{BEGIN}
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* GRASP-type PDZ domain profile *
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The Golgi  apparatus is a highly dynamic organelle responsible for sorting out
proteins and  other  biomolecules to the cell surface and to the extracellular
milieu. The   Golgi   apparatus   is  comprised  of  flattened  membrane-bound
compartments called  cisternae,  which  are  apposed  to one another to form a
Golgi stack.  The  structural  organization  of  the cisternae into stacks and
their lateral  connection,  building  the  Golgi  ribbon, requires a family of
proteins called Golgi ReAssembly and Stacking Proteins (GRASP). Two homologues
(GRASP55 and  GRASP65)  have been described in vertebrates and their functions
have been  associated to Golgi phosphorylation-regulated assembly/disassembly,
protein secretion  ,  Golgi remodeling in migrating cells, among others. There
is only one gene for GRASP in lower eukaryotes. Essentially all GRASPs contain
a conserved  N-terminal  GRASP  region, which comprises two tandem PDZ domains
(PDZ1 and   PDZ2),   a   classical  protein-peptide  interaction  domain  (see
<PDOC50106>), and  is  responsible  for GRASP homo-oligomerization and for the
attachment to  the  Golgi membrane. The C-terminal half which is not conserved
between species  but  is  rich  in  proline  and  serines residues, as well as
glutamine and asparagine residues [1,2,3,4].

The GRASP-type  PDZ domains adopt a canonical PDZ fold with a beta-sandwich of
five beta-strands  and  two  alpha-helices (see <PDB:4KFW>). The PDZ1 and PDZ2
domains are  nearly  superimposable.  The  peptide-binding pockets of both PDZ
domains are  formed by alpha2 and beta5. A typical ligand peptide is predicted
to form   antiparallel   beta-strand   interactions   with  beta5  and  insert
hydrophobic side  chains  between  alpha2  and  beta5.  The  two  PDZ  domains
cooperate to  achieve dimerization and oligomerization. In the dimers the PDZ2
domains interact  in  a  way that positions the peptide-binding pockets facing
each other.  In  addition,  the dimers are linked through interactions between
the two C-terminal tails (CTs) of one dimer and two peptide-binding pockets of
the PDZ1 domains in the next dimer [3,4].

The profile we developed covers the entire GRASP-type PDZ domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2018 / First entry.

[ 1] Mendes L.F.S., Garcia A.F., Kumagai P.S., de Morais F.R., Melo F.A.,
     Kmetzsch L., Vainstein M.H., Rodrigues M.L., Costa-Filho A.J.
     "New structural insights into Golgi Reassembly and Stacking Protein
     (GRASP) in solution."
     Sci. Rep. 6:29976-29976(2016).
     PubMed=27436376; DOI=10.1038/srep29976
[ 2] Vinke F.P., Grieve A.G., Rabouille C.
     "The multiple facets of the Golgi reassembly stacking proteins."
     Biochem. J. 433:423-433(2011).
     PubMed=21235525; DOI=10.1042/BJ20101540
[ 3] Feng Y., Yu W., Li X., Lin S., Zhou Y., Hu J., Liu X.
     "Structural insight into Golgi membrane stacking by GRASP65 and
     GRASP55 proteins."
     J. Biol. Chem. 288:28418-28427(2013).
     PubMed=23940043; DOI=10.1074/jbc.M113.478024
[ 4] Truschel S.T., Sengupta D., Foote A., Heroux A., Macbeth M.R.,
     Linstedt A.D.
     "Structure of the membrane-tethering GRASP domain reveals a unique PDZ
     ligand interaction that mediates Golgi biogenesis."
     J. Biol. Chem. 286:20125-20129(2011).
     PubMed=21515684; DOI=10.1074/jbc.C111.245324

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