6l4o

From Proteopedia

Jump to: navigation, search

Crystal structure of API5-FGF2 complex

Structural highlights

6l4o is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

API5_HUMAN Antiapoptotic factor that may have a role in protein assembly. Negatively regulates ACIN1. By binding to ACIN1, it suppresses ACIN1 cleavage from CASP3 and ACIN1-mediated DNA fragmentation. Also known to efficiently suppress E2F1-induced apoptosis. Its depletion enhances the cytotoxic action of the chemotherapeutic drugs.[1] [2] [3]

Publication Abstract from PubMed

API5 (APoptosis Inhibitor 5) and nuclear FGF2 (Fibroblast Growth Factor 2) are upregulated in various human cancers and are correlated with poor prognosis. Although their physical interaction has been identified, the function related to the resulting complex is unknown. Here, we determined the crystal structure of the API5-FGF2 complex and identified critical residues driving the protein interaction. These findings provided a structural basis for the nuclear localization of the FGF2 isoform lacking a canonical nuclear localization signal and identified a cryptic nuclear localization sequence in FGF2. The interaction between API5 and FGF2 was important for mRNA nuclear export through both the TREX and eIF4E/LRPPRC mRNA export complexes, thus regulating the export of bulk mRNA and specific mRNAs containing eIF4E sensitivity elements, such as c-MYC and cyclin D1. These data show the newly identified molecular function of API5 and nuclear FGF2, and provide a clue to understanding the dynamic regulation of mRNA export.

Regulation of mRNA export through API5 and nuclear FGF2 interaction.,Bong SM, Bae SH, Song B, Gwak H, Yang SW, Kim S, Nam S, Rajalingam K, Oh SJ, Kim TW, Park S, Jang H, Lee BI Nucleic Acids Res. 2020 Jun 19;48(11):6340-6352. doi: 10.1093/nar/gkaa335. PMID:32383752[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
3 reviews cite this structure
Types of nuclear localization signals and mechanisms of protein import into the nucleus.
Lu et al. (2021)
2 more
14 other articles
No citations found

See Also

References

  1. ↑ Kim JW, Cho HS, Kim JH, Hur SY, Kim TE, Lee JM, Kim IK, Namkoong SE. AAC-11 overexpression induces invasion and protects cervical cancer cells from apoptosis. Lab Invest. 2000 Apr;80(4):587-94. PMID:10780674
  2. ↑ Morris EJ, Michaud WA, Ji JY, Moon NS, Rocco JW, Dyson NJ. Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet. 2006 Nov 17;2(11):e196. PMID:17112319 doi:06-PLGE-RA-0285R2
  3. ↑ Rigou P, Piddubnyak V, Faye A, Rain JC, Michel L, Calvo F, Poyet JL. The antiapoptotic protein AAC-11 interacts with and regulates Acinus-mediated DNA fragmentation. EMBO J. 2009 Jun 3;28(11):1576-88. doi: 10.1038/emboj.2009.106. Epub 2009 Apr 23. PMID:19387494 doi:10.1038/emboj.2009.106
  4. ↑ Bong SM, Bae SH, Song B, Gwak H, Yang SW, Kim S, Nam S, Rajalingam K, Oh SJ, Kim TW, Park S, Jang H, Lee BI. Regulation of mRNA export through API5 and nuclear FGF2 interaction. Nucleic Acids Res. 2020 Jun 19;48(11):6340-6352. doi: 10.1093/nar/gkaa335. PMID:32383752 doi:http://dx.doi.org/10.1093/nar/gkaa335

Contents


PDB ID 6l4o

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/6l4o"
Personal tools