PDBsum entry 2kum

Signaling protein

PDB id: 2kum

Contents

Protein chain

88 a.a. *

* Residue conservation analysis

PDB id:

2kum

Name:

Signaling protein

Title:

Solution structure of the human chemokine ccl27

Structure:

C-c motif chemokine 27. Chain: a. Synonym: small-inducible cytokine a27, cc chemokine ilc, il-11 r- alpha-locus chemokine, skinkine, eskine, cutaneous t-cell-attracting chemokine, ctack. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: alp, ccl27, ctack, ctak, eskine, ilc, pesky, scya27. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

30 models

Authors:

J.P.Kirkpatrick,A.Jansma,A.Hsu,T.M.Handel,D.Nietlispach

Key ref:

A.L.Jansma et al. (2010). NMR analysis of the structure, dynamics, and unique oligomerization properties of the chemokine CCL27. J Biol Chem, 285, 14424-14437. PubMed id: 20200157

Date:

22-Feb-10 Release date: 02-Mar-10

Protein chain

Q9Y4X3  (CCL27_HUMAN) -  C-C motif chemokine 27 from Homo sapiens

Seq: 112 a.a.

Struc: 88 a.a.

J Biol Chem 285:14424-14437 (2010)

PubMed id: 20200157

NMR analysis of the structure, dynamics, and unique oligomerization properties of the chemokine CCL27.

A.L.Jansma, J.P.Kirkpatrick, A.R.Hsu, T.M.Handel, D.Nietlispach.

ABSTRACT

Chemokines have two essential interactions in vivo, with G protein-coupled receptors, which activate intracellular signaling pathways, and with glycosaminoglycans (GAGs), which are involved in cell surface localization and transport. Although it has been shown that chemokines bind and activate their respective G protein-coupled receptors as monomers, many chemokines oligomerize upon GAG binding, and the ability to oligomerize and bind GAGs is required for in vivo function. In this study, we investigated the structure, dynamics, and oligomerization behavior of cutaneous T-cell-attracting chemokine (CTACK, also known as CCL27) by NMR. (15)N relaxation and translational self-diffusion rates indicate that CCL27 oligomerizes, but in contrast to many other chemokines that form relatively discrete oligomers, CCL27 transitions between monomer, dimer, and tetramer species over a relatively narrow concentration range. A three-dimensional structure determination was pursued under conditions where CCL27 is primarily dimeric, revealing the standard motif for a chemokine monomer. Analysis of chemical shift perturbations of (1)H-(15)N HSQC spectra, relaxation-dispersion experiments, and filtered nuclear Overhauser effects suggest that CCL27 does not adopt a discrete CXC or CC dimer motif. Instead, CCL27 has uncommon oligomerization behavior, where several equilibria involving relatively low affinity interactions between different interfaces seem to be simultaneously at work. However, interaction with heparin avidly promotes oligomerization under conditions where CCL27 is monomeric by itself. We hypothesize that the plasticity in the oligomerization state may enable CCL27 to adopt different oligomeric structures, depending on the nature of the GAG binding partner, thereby providing a mechanism for increased diversity and specificity in GAG-binding and GAG-related functions.