2q8r
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /> <applet load="2q8r" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q8r, resolution 1.820Å" /> '''Structural and Fun...)
Next diff →
Revision as of 21:24, 12 November 2007
|
Structural and Functional Characterization of CC Chemokine CCL14
Overview
CC chemokine ligand 14, CCL14, is a human CC chemokine that is of recent, interest because of its natural ability, upon proteolytic processing of, the first eight NH2-terminal residues, to bind to and signal through the, human immunodeficiency virus type-1 (HIV-1) co-receptor, CC chemokine, receptor 5 (CCR5). We report X-ray crystallographic structures of both, full-length CCL14 and signaling-active, truncated CCL14 [9-74] determined, at 2.23 and 1.8 A, respectively. Although CCL14 and CCL14 [9-74] differ in, their ability to bind CCR5 for biological signaling, we find that the, NH2-terminal eight amino acids (residues 1 through 8) are completely, disordered in CCL14 and both show the identical mode of the dimeric, assembly characteristic of the CC type chemokine structures. However, analytical ultracentrifugation studies reveal that the CCL14 is stable as, a dimer at a concentration as low as 100 nM, whereas CCL14 [9-74] is fully, monomeric at the same concentration. By the same method, the equilibrium, between monomers of CCL14 [9-74] and higher order oligomers is estimated, to be of EC1,4 = 4.98 muM for monomer-tetramer conversion. The relative, instability of CCL14 [9-74] oligomers as compared to CCL14 is also, reflected in the Kd's that are estimated by the surface plasmon resonance, method to be approximately 9.84 and 667 nM for CCL14 and CCL14 [9-74], respectively. This approximately 60-fold difference in stability at a, physiologically relevant concentration can potentially account for their, different signaling ability. Functional data from the activity assays by, intracellular calcium flux and inhibition of CCR5-mediated HIV-1 entry, show that only CCL14 [9-74] is fully active at these near-physiological, concentrations where CCL14 [9-74] is monomeric and CCL14 is dimeric. These, results together suggest that the ability of CCL14 [9-74] to monomerize, can play a role for cellular activation.
About this Structure
2Q8R is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and Functional Characterization of CC Chemokine CCL14(,)., Blain KY, Kwiatkowski W, Zhao Q, Fleur DL, Naik C, Chun TW, Tsareva T, Kanakaraj P, Laird MW, Shah R, George L, Sanyal I, Moore PA, Demeler B, Choe S, Biochemistry. 2007 Sep 4;46(35):10008-10015. Epub 2007 Aug 11. PMID:17691823
Page seeded by OCA on Mon Nov 12 23:31:19 2007
