AP2 adaptor complex

Quality 0.50 · 2 views · Updated 2 months ago

title: "AP2 adaptor complex" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["peripheral-membrane-proteins", "vesicular-transport-proteins"] topic_path: "sports" source: "https://en.wikipedia.org/wiki/AP2_adaptor_complex" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::figure[src="https://upload.wikimedia.org/wikipedia/commons/f/f9/AP-2_complex.png" caption="internalisation]]. The alpha and beta appendage domains bind to accessory proteins and to [[clathrin]]. Their interactions allow the temporal and spatial regulation of the assembly of [[clathrin-coated vesicles]] and their [[endocytosis]]."] ::

The AP-2 complex is a heterotetramer consisting of two large adaptins (α and β), a medium adaptin (μ), and a small adaptin (σ):

Structure

The AP2 adaptor complex exists in two primary conformations: the open conformation (active state) and the closed conformation (inactive state). In its active state, the clathrin binding site found on the β subunit and the cargo binding site found on the μ subunit are exposed to the cytosol, allowing their respective interactions to occur. In its inactive state, the complex experiences a conformational change that causes both sites to be covered, preventing its primary functions. The α and β heavy chains of the complex make up about 60% of the polypeptide sequence of AP2 and are tightly structured into 14 HEAT repeats which form zigzagging α-helical structures that interact with the helical "legs" of the clathrin trimer. ::figure[src="https://upload.wikimedia.org/wikipedia/commons/f/fb/Ap2colorcropped.jpg" caption="doi-access = free }} Red - alpha subunits. Blue - beta subunit. Green - mu subunit. Yellow - sigma subunit."] ::

Function

AP2 facilitates the assembly of clathrin lattices when endocytosis needs to occur, by aggregating together with other AP2 complexes, in their active conformation. These AP2 aggregates interact with individual clathrin proteins by their β-active sites, orienting them into the clathrin "cages" that form the endocytic coat.

Regulation

The regulation of AP2 activity is primarily done through conformational rearrangements of the structure into two distinct (and a potential third and fourth) conformations. The "open" conformation is the active state of the complex, as the "pits" or active binding sites for clathrins and the cargo are uncovered. On the other hand, the "closed" conformation is denoted by the closing or inaccessibility of these same sites.

Activation

The presence of clathrins have been found to induce binding to cargo, and similarly, presence of cargo appears to induce clathrin binding. This is thought to occur by a secondary stabilization of the complex structure, which would allow partial activation, or access, to the respective pits. Phosphatidylinositol-(4,5)-bisphosphate (PIP2) serves as a signal sequence that binds and is recognized by AP2. PIP2 can be found within liposomes containing cargo, which interact with AP2 to then bind clathrin and execute its function. In the closed form, the PIP2 binding site is exposed, allowing for the conformational regulation to occur. Because of this, a certain order of slight conformational changes bring about the fully open conformation, beginning with PIP2 binding, then cargo sequence binding, and finally clathrin binding. A family of proteins called muniscins are thought to be the primary allosteric activators of the AP2 adaptor complex, due to their prevalence in AP2 associated pits and their inhibition resulting in the decrease in AP2 mediated endocytosis. Additionally, the complex has been found to be regulated and activated by phosphorylation of its (mu) subunit.

Deactivation

Deactivation, or change into the "closed" conformation, is still unclear. NECAPs are thought the play a role in it, by binding to the α subunit of AP2. Not much is known, but the open conformation of AP2, which is phosphorylated, appears to be necessary for NECAP1 to bind within its core. The process of action is still unknown, but this interaction causes the dephosphorylation of the AP2 adaptor complex, thus deactivating it.

Medical Relevance

AP2 has been identified to intimately participate in autophagic cellular pathways, responsible for the degradation of aggregated protein. In fact, it's seen to complex with phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM), which would serve as an important receptor group for microtubule-associated protein 1 light chain 3 (LC3). LC3 has an important role in some autophagic pathways. Because of this, there is suspicion that AP2 deficiency or dysfunction may be a precursor for the development of familial Alzheimer's Disease.

References

References

  1. (April 2000). "Clathrin coat construction in endocytosis". Current Opinion in Structural Biology.
  2. (2002-05-17). "Molecular Architecture and Functional Model of the Endocytic AP2 Complex". Cell.
  3. (January 2018). "NECAPs are negative regulators of the AP2 clathrin adaptor complex". eLife.
  4. (May 2014). "Molecular structure, function, and dynamics of clathrin-mediated membrane traffic". Cold Spring Harbor Perspectives in Biology.
  5. (August 2019). "A structural mechanism for phosphorylation-dependent inactivation of the AP2 complex". eLife.
  6. (October 2019). "Conformational regulation of AP1 and AP2 clathrin adaptor complexes". Traffic.
  7. (September 2004). "Endocytosis by random initiation and stabilization of clathrin-coated pits". Cell.
  8. (May 1997). "Regulatory interactions in the recognition of endocytic sorting signals by AP-2 complexes". The EMBO Journal.
  9. (January 2017). "Regulation of clathrin-mediated endocytosis by hierarchical allosteric activation of AP2". The Journal of Cell Biology.
  10. (October 2009). "Syp1 is a conserved endocytic adaptor that contains domains involved in cargo selection and membrane tubulation". The EMBO Journal.
  11. (June 2010). "FCHo proteins are nucleators of clathrin-mediated endocytosis". Science.
  12. (August 2012). "The first five seconds in the life of a clathrin-coated pit". Cell.
  13. (March 2003). "AP-1 binding to sorting signals and release from clathrin-coated vesicles is regulated by phosphorylation". The Journal of Cell Biology.
  14. (March 2002). "Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals". The Journal of Cell Biology.
  15. (October 2013). "Adaptor complex AP2/PICALM, through interaction with LC3, targets Alzheimer's APP-CTF for terminal degradation via autophagy". Proceedings of the National Academy of Sciences of the United States of America.
  16. (2018). "Retinal Degenerative Diseases".

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::

peripheral-membrane-proteinsvesicular-transport-proteins