| Structural highlights
4dkl is a 1 chain structure with sequence from Escherichia virus T4 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Method: | X-ray diffraction, Resolution 2.8Å |
Ligands: | , , , , , |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
OPRM_MOUSE Receptor for endogenous opioids such as beta-endorphin and endomorphin. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 9 is involved in morphine-induced scratching and seems to cross-activate GRPR in response to morphine.[1] [2] [3] [4] [5] [6] ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[7]
See Also
References
- ↑ George SR, Fan T, Xie Z, Tse R, Tam V, Varghese G, O'Dowd BF. Oligomerization of mu- and delta-opioid receptors. Generation of novel functional properties. J Biol Chem. 2000 Aug 25;275(34):26128-35. PMID:10842167 doi:http://dx.doi.org/10.1074/jbc.M000345200
- ↑ Rios C, Gomes I, Devi LA. mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis. Br J Pharmacol. 2006 Jun;148(4):387-95. Epub 2006 May 8. PMID:16682964 doi:http://dx.doi.org/10.1038/sj.bjp.0706757
- ↑ Milan-Lobo L, Whistler JL. Heteromerization of the mu- and delta-opioid receptors produces ligand-biased antagonism and alters mu-receptor trafficking. J Pharmacol Exp Ther. 2011 Jun;337(3):868-75. doi: 10.1124/jpet.111.179093. Epub , 2011 Mar 21. PMID:21422164 doi:http://dx.doi.org/10.1124/jpet.111.179093
- ↑ Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S. Crystal structure of the micro-opioid receptor bound to a morphinan antagonist. Nature. 2012 Mar 21. doi: 10.1038/nature10954. PMID:22437502 doi:10.1038/nature10954
- ↑ Kaufman DL, Keith DE Jr, Anton B, Tian J, Magendzo K, Newman D, Tran TH, Lee DS, Wen C, Xia YR, et al.. Characterization of the murine mu opioid receptor gene. J Biol Chem. 1995 Jun 30;270(26):15877-83. PMID:7797593
- ↑ Sora I, Takahashi N, Funada M, Ujike H, Revay RS, Donovan DM, Miner LL, Uhl GR. Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1544-9. PMID:9037090
- ↑ Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:http://dx.doi.org/10.1002/pro.2042
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