| Structural highlights
Function
[IDE_HUMAN] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.[1] [2] [3] [CCL4_HUMAN] Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B.[4] [5] [6]
References
- ↑ Vekrellis K, Ye Z, Qiu WQ, Walsh D, Hartley D, Chesneau V, Rosner MR, Selkoe DJ. Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme. J Neurosci. 2000 Mar 1;20(5):1657-65. PMID:10684867
- ↑ Im H, Manolopoulou M, Malito E, Shen Y, Zhao J, Neant-Fery M, Sun CY, Meredith SC, Sisodia SS, Leissring MA, Tang WJ. Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE. J Biol Chem. 2007 Aug 31;282(35):25453-63. Epub 2007 Jul 5. PMID:17613531 doi:10.1074/jbc.M701590200
- ↑ Malito E, Ralat LA, Manolopoulou M, Tsay JL, Wadlington NL, Tang WJ. Molecular Bases for the Recognition of Short Peptide Substrates and Cysteine-Directed Modifications of Human Insulin-Degrading Enzyme. Biochemistry. 2008 Nov 6. PMID:18986166 doi:10.1021/bi801192h
- ↑ Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811-5. PMID:8525373
- ↑ Garlisi CG, Xiao H, Tian F, Hedrick JA, Billah MM, Egan RW, Umland SP. The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8. Eur J Immunol. 1999 Oct;29(10):3210-5. PMID:10540332 doi:http://dx.doi.org/10.1002/(SICI)1521-4141(199910)29:10<3210::AID-IMMU3210>3.0.CO;2-W
- ↑ Guan E, Wang J, Roderiquez G, Norcross MA. Natural truncation of the chemokine MIP-1 beta /CCL4 affects receptor specificity but not anti-HIV-1 activity. J Biol Chem. 2002 Aug 30;277(35):32348-52. Epub 2002 Jun 17. PMID:12070155 doi:http://dx.doi.org/10.1074/jbc.M203077200
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