Here, using single-molecule FRET, we reveal previously hidden conformations of the ankyrin-repeat domain of AnkyrinR, a giant adaptor molecule that anchors integral membrane proteins to the spectrin-actin cytoskeleton through simultaneous binding of multiple partner proteins.
This approach focuses on essential cellular functionalities, which can be carried out by multiple partner proteins - for example, isoenzymes.
The ability of FHL2 to assemble multiple partners into protein complexes is attributed to its LIM-domain structure that serves as protein binding interface through double zinc finger motifs [17].
LAT then becomes a scaffold protein for the recruitment of multiple partners including the adaptor proteins Gads and Grb2 and the enzymes of phospholipid metabolism phosphatidylinositol-3 kinase and PLCγ1 [ 24].
A recent publication confirmed that many members of the PDI family, including PDI, PDIr, ERp57, ERp72, P5, ERdj5 and ERp29, make multiple interactions with partner proteins within the ER ([ 45] see, for example, Figure 2A in this reference).
LIM proteins could have multiple partners in the cell, such as actin or tubulin cytoskeleton, DNA and other potential proteins.
In some cases these proteins can bind multiple partners, which can lead to distinct structures and promiscuity in functions.
However, besides PCNA and UHRF1 proteins, DNMT1 has multiple partners of interaction, the loss of which could potentially promote the initiation of tumorigenesis or progression via the generation of the global DNA hypomethylation phenotype.
We pointed out earlier that intrinsic disorder could enable one protein to associate with multiple partners (one-to-many signaling) and could also enable multiple partners to associate with one protein (many-to-one signaling) [ 35].
We defined IRs that shared 50% or more of their targets with other IRs obtained from different bait proteins as IRs with multiple partners.
