4oz1
From Proteopedia
Crystal structure of human CAPERalpha UHM bound to SF3b155 ULM5
Structural highlights
Function[RBM39_HUMAN] Transcriptional coactivator for steroid nuclear receptors ESR1/ER-alpha and ESR2/ER-beta, and JUN/AP-1 (By similarity). May be involved in pre-mRNA splicing process. [SF3B1_HUMAN] Subunit of the splicing factor SF3B required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. May also be involved in the assembly of the 'E' complex. Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron. Publication Abstract from PubMedU2AF Homology Motifs (UHMs) mediate protein-protein interactions with U2AF Ligand Motifs (ULMs) of pre-mRNA splicing factors. The UHM-containing alternative splicing factor CAPERalpha regulates splicing of tumor-promoting VEGF isoforms, yet the molecular target of the CAPERalpha UHM is unknown. Here, we present structures of the CAPERalpha UHM bound to a representative SF3b155 ULM at 1.7 A resolution, and for comparison, in the absence of ligand at 2.2 A resolution. The prototypical UHM/ULM interactions authenticate CAPERalpha as a bona fide member of the UHM-family of proteins. We identify SF3b155 as the relevant ULM-containing partner of full-length CAPERalpha in human cell extracts. Isothermal titration calorimetry comparisons of the purified CAPERalpha UHM binding known ULM-containing proteins demonstrate that high affinity interactions depend on the presence of an intact, intrinsically-unstructured SF3b155 domain containing seven ULM-like motifs. The interplay among bound CAPERalpha molecules gives rise to the appearance of two high affinity sites in the SF3b155 ULM-containing domain. In conjunction with the previously-identified, UHM/ULM-mediated complexes of U2AF65 and SPF45 with SF3b155, this work demonstrates the capacity of SF3b155 to offer a platform for coordinated recruitment of UHM-containing splicing factors. Cancer-Relevant Splicing Factor CAPERalpha Engages the Essential Splicing Factor SF3b155 in a Specific Ternary Complex.,Loerch S, Maucuer A, Manceau V, Green MR, Kielkopf CL J Biol Chem. 2014 May 2. PMID:24795046[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
