Shank protein: Difference between revisions
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The **canonical PDZ domain** contains 90 amino acids and folds into a compact **globular structure** consisting of a six-stranded β-sandwich flanked by two alpha helices.<ref name="IM"/> βPIX forms a **parallel trimer** via **helical interactions** within its CC domain, and with a **PDZ binding domain** at the C-terminus. Interestingly, only 1 Shank molecule is bound to the CC domain trimer of βPIX in an **asymettric assembly**. (SHOW ZOOMED OUT IN SPACE FILL WITH LONG PART DIRECTLY VERTICAL) The **8-residue PDZ binding domain** (BALL AND STICK AND SPHERE COMBO BURIED MODE) of βPIX forms a number of **hydrogen bonding and hydrophobic interactions** (FIGURE 2A) with the Shank PDZ domain. Shank3-Arg 679 forms the **most critical interaction** with βPIX, tightly binding Glutamate -3. Abolishing this interaction through mutagenesis completely eliminates the assembly. Upon binding of βPIX, the PDZ domain undergoes a significant **conformational change** (OVERVIEW MORPH). Lys 682 undergoes a nearly **11 Angstrom displacement**, ultimately forming a **beta-sheet interaction**, with βPIX residues -4--6, incorporating Shank residues 680 and 681.<ref name="IM"/> | The **canonical PDZ domain** contains 90 amino acids and folds into a compact **globular structure** consisting of a six-stranded β-sandwich flanked by two alpha helices.<ref name="IM"/> βPIX forms a **parallel trimer** via **helical interactions** within its CC domain, and with a **PDZ binding domain** at the C-terminus. Interestingly, only 1 Shank molecule is bound to the CC domain trimer of βPIX in an **asymettric assembly**. (SHOW ZOOMED OUT IN SPACE FILL WITH LONG PART DIRECTLY VERTICAL) The **8-residue PDZ binding domain** (BALL AND STICK AND SPHERE COMBO BURIED MODE) of βPIX forms a number of **hydrogen bonding and hydrophobic interactions** (FIGURE 2A) with the Shank PDZ domain. Shank3-Arg 679 forms the **most critical interaction** with βPIX, tightly binding Glutamate -3. Abolishing this interaction through mutagenesis completely eliminates the assembly. Upon binding of βPIX, the PDZ domain undergoes a significant **conformational change** (OVERVIEW MORPH). Lys 682 undergoes a nearly **11 Angstrom displacement**, ultimately forming a **beta-sheet interaction**, with βPIX residues -4--6, incorporating Shank residues 680 and 681.<ref name="IM"/> | ||
Shank proteins are wedged between scaffolding proteins that are bound to either neurotransmitter receptors or the actin cytoskeleton, making them well positioned to nucleate the underlying structure of the PSD.<ref name="Baron"/> The SAM domain of <scene name='Shank_Family_Proteins/Multimer_opening/1'>Shank3 can oligomerize</scene> (<scene name='Shank_Family_Proteins/Multimer_opening_alt/ | Shank proteins are wedged between scaffolding proteins that are bound to either neurotransmitter receptors or the actin cytoskeleton, making them well positioned to nucleate the underlying structure of the PSD.<ref name="Baron"/> The SAM domain of <scene name='Shank_Family_Proteins/Multimer_opening/1'>Shank3 can oligomerize</scene> (<scene name='Shank_Family_Proteins/Multimer_opening_alt/2'>Alternate View</scene>) to form large sheets composed of helical fibers stacked side by side. The proposed sheet structure with radially projecting protein interaction domains, appears to be an ideal architecture for a protein that must contact both membrane and cytoplasmic components at a cell surface.<ref name="Baron"/> Models of this sort validate the importance of Shank3 as master scaffolding proteins and illustrate how slight mutations can disrupt an entire PSD and synaptic function. | ||
</StructureSection> | </StructureSection> | ||
==Additional Structures of Shank Family Proteins== | ==Additional Structures of Shank Family Proteins== | ||
==References== | ==References== | ||
<references/> | <references/> | ||