Structure of CRL2APPBP2 bound with RxxGP degron (dimer)Structure of CRL2APPBP2 bound with RxxGP degron (dimer)

Structural highlights

8jal is a 10 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:Electron Microscopy, Resolution 3.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

APBP2_HUMAN Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:29775578). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29779948, PubMed:29775578). The CRL2(APPBP2) complex specifically recognizes proteins with a -Arg-Xaa-Xaa-Gly degron at the C-terminus, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:29775578). The CRL2(APPBP2) complex mediates ubiquitination and degradation of truncated SELENOV selenoproteins produced by failed UGA/Sec decoding, which end with a -Arg-Xaa-Xaa-Gly degron (PubMed:26138980). May play a role in intracellular protein transport: may be involved in the translocation of APP along microtubules toward the cell surface (PubMed:9843960).[1] [2] [3] [4]

References

  1. Lin HC, Ho SC, Chen YY, Khoo KH, Hsu PH, Yen HC. SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding. Science. 2015 Jul 3;349(6243):91-5. PMID:26138980 doi:10.1126/science.aab0515
  2. Lin HC, Yeh CW, Chen YF, Lee TT, Hsieh PY, Rusnac DV, Lin SY, Elledge SJ, Zheng N, Yen HS. C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases. Mol Cell. 2018 May 17;70(4):602-613.e3. PMID:29775578 doi:10.1016/j.molcel.2018.04.006
  3. Koren I, Timms RT, Kula T, Xu Q, Li MZ, Elledge SJ. The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons. Cell. 2018 Jun 14;173(7):1622-1635.e14. PMID:29779948 doi:10.1016/j.cell.2018.04.028
  4. Zheng P, Eastman J, Vande Pol S, Pimplikar SW. PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14745-50. PMID:9843960 doi:10.1073/pnas.95.25.14745

8jal, resolution 3.30Å

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