Cancer-relevant splicing factor CAPERα engages the essential splicing factor SF3b155 in a specific ternary complex.

摘要: U2AF homology motifs (UHMs) mediate protein-protein interactions with ligand (ULMs) of pre-mRNA splicing factors. The UHM-containing alternative factor CAPERα regulates tumor-promoting VEGF isoforms, yet the molecular target UHM is unknown. Here we present structures bound to a representative SF3b155 ULM at 1.7 Å resolution and, for comparison, in absence 2.2 resolution. prototypical UHM/ULM authenticate as bona fide member family proteins. We identify relevant ULM-containing partner full-length human cell extracts. Isothermal titration calorimetry comparisons purified binding known proteins demonstrate that high affinity depend on presence an intact, intrinsically unstructured domain containing seven ULM-like motifs. interplay among molecules gives rise appearance two sites domain. In conjunction previously identified, UHM/ULM-mediated complexes U2AF65 and SPF45 SF3b155, this work demonstrates capacity offer platform coordinated recruitment