Configurations of LIR motifs within protein interaction hotspots. A single representative example of each configuration is shown below. Additional examples corresponding to each category are listed in Table 1. (a) Adjacent: Distinct motifs located in close proximity, allowing independently mediated interactions with two or more binding partners. Due to their proximity and/or conformational requirements, these interactions often exhibit cooperative or competitive binding. The NBR1 interaction with Atg8s and TAX1BP1 is an example of competitive binding. (b) Bipartite: Binding requires both the LIR motif and additional residues, either N- or C-terminal, surrounding the LIR. (c) Hybrid: Overlapping binding sites enable interactions with multiple partners. This configuration often involves a tradeoff in binding specificity or affinity.