Signal transducing adaptor proteins (STAPs) are proteins that aids in the major proteins in a very signal transduction pathway. Adaptor proteins contain various protein-binding modules that link protein-binding partners together to promote the production of larger signal complexes. These proteins often lack any intrinsic enzymatic activity themselves rather than mediating specific protein-protein interactions that promote the formation of protein complexes. Examples of adaptor proteins include MYD88, Grb2 and SHC1. Adaptor proteins usually contain several domains within their structure that permit specific interactions with some other specific proteins. The SH2 domain recognizes specific amino acid sequences in proteins that containing phosphotyrosine residues, and the SH3 domain recognizes proline-rich sequences in the context of a protein-specific peptide sequence. There are many other sorts of interaction domains observed in adaptor and other signalling proteins that allow a rich diversity of specific and coordinated protein-protein interactions to occur within the cell during signal transduction. Much of the specificity of signal transduction relies on the recruitment of many signalling components such as protein kinases and G-protein GTPases into short-lived active complexes in response to an activating signal such as a growth factor binding to its receptor.
Figure 1. Src-associated adaptor protein Skap2 with 1u5e code.
Vesicular transport adaptor protein
Vesicular transport adaptor proteins are proteins involved in forming complexes that function in the trafficking of molecules from one subcellular location to another. These complexes concentrate the correct cargo molecules in vesicles that bud or extrude off of one organelle and travel to another location, where the cargo is delivered. While some of the details of how these adaptor proteins achieve their trafficking specificity has been worked out, there is still much to be learned. There are several human disorders associated with defects in components of these complexes including Alzheimer's and Parkinson's diseases. Alzheimer's disease (AD), also referred to simply as Alzheimer's, is a chronic neurodegenerative disease that usually starts slowly and gradually worsens over time.It is the cause of 60-70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, not managing selfcare, and behavioural issues. Most of the adaptor proteins are heterotetramers. The AP complexes contains two large proteins and two smaller proteins.
AP-2/CCVs are involved in autosomal recessive hypercholesterolemia through the associated low-density lipoprotein receptor adapter protein 1. Retromer is involved in recycling components of the plasma membrane. The importance of that recycling at a synapse is hinted at in one of the figures in the gallery. There are at least 3 ways in which retromer dysfunction can contribute to brain disorders, including Alzheimer and Parkinson diseases. AP-5 is the most recently described complex, and one reason supporting the idea that it is an authentic adaptor complex is that it is associated with hereditary spastic paraplegia, as is AP-4. AP-1 is linked to MEDNIK syndrome. AP-3 is linked to Hermansky-Pudlak syndrome. One of the GGA proteins may be involved in Alzheimer's disease.
1. Jackson LP.; et al. Structure and mechanism of COPI vesicle biogenesis. Current Opinion in Cell Biology. 2014, 29: 67-73
2. Burd C.; et al. "Retromer: a master conductor of endosome sorting. Cold Spring Harbor Perspectives in Biology. 2014, 6 (2): a016774.