Solution Structure of CCL19 and Identification of Overlapping CCR7 and PSGL-1 Binding Sites

Veldkamp, Christopher T.; Kiermaier, Eva; Gabel-Eissens, S.J.; Gillitzer, M.L.; Lippner, David; DiSilvio, Frank; Mueller, Casey J.; Wantuch, Paeton L; Chaffee, Gary R.; Famiglietti, Michael W.; Zgoba, Danielle M.; Bailey, Asha A.; Bah, Yaya; Engebretson, Samantha J.; Graupner, David R.; Lackner, Emily R.; LaRosa, Vincent D.; Medeiros, Tysha N.; Olson, Michael; Phillips, Andrew J.; Pyles, Harley; Richard, Amanda M; Schoeller, Scott J.; Touzeau, Boris; Williams, Larry G.; Sixt, Michael; Peterson, Francis C.

doi:10.1021/acs.biochem.5b00560

Cited by 36 publications

(70 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…100 µM U- 15 N labeled CCL21 in 25 mM deuterated MES pH 6.0, 10% D 2 O, and 0.2% NaN 3 was titrated with heparin disaccharide I-S (Sigma–Aldrich) and monitored using 15 N- 1 H HSQC spectra as previously described [19, 25]. Combined amide chemical shift perturbations were computed as [(Δδ H ) 2 +(Δδ N ) 2 ] 1/2 , where Δδ H and Δδ N are changes in backbone amide 1 H and 15 N chemical shifts in ppm, respectively.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Transferring the C-terminus of the chemokine CCL21 to CCL19 confers enhanced heparin binding

Barmore

Castex

Gouletas

et al. 2016

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

Chemokines direct the migration of cells during various immune processes and are involved in many disease states. For example, CCL19 and CCL21, through activation of the CCR7 receptor, recruit dendritic cells and naïve T-cells to the secondary lymphoid organs aiding in balancing immune response and tolerance. However, CCL19 and CCL21 can also direct the metastasis of CCR7 expressing cancers. Chemokine binding to glycosaminoglycans, such as heparin, is as important to chemokine function as receptor activation. CCL21 is unique in that it contains an extended C-terminus not found in other chemokines like CCL19. Deletion of this extended C-terminus reduces CCL21’s affinity for heparin and transferring the CCL21 C-terminus to CCL19 enhances heparin binding mainly through non-specific, electrostatic interactions.

show abstract

Section: Methodsmentioning

confidence: 99%

“…The domain is often followed by a very short flexible C-terminus [18]. For example, CCL19 contains 77 residues with the seven most C-terminal residues making up the short unstructured C-terminus [19]. CCL21 contains a chemokine domain but residues 71–111 are unstructured with the exception of a disulfide bond linking C80 to C99 [20].…”

Section: Introductionmentioning

confidence: 99%

Transferring the C-terminus of the chemokine CCL21 to CCL19 confers enhanced heparin binding

Barmore

Castex

Gouletas

et al. 2016

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

show abstract

“…2. Mammalian CCL19 has a canonical chemokine fold consisting of a flexible N-terminus and N-loop followed by an antiparallel three stranded β-sheet, a C-terminal α-helix, and a short flexible C-terminus (65). Predicted rainbow trout CCL19-like structures show some commonalities but also important differences compared to mammalian CCL19.…”

Section: Resultsmentioning

confidence: 99%

CK12a, a CCL19-like Chemokine That Orchestrates both Nasal and Systemic Antiviral Immune Responses in Rainbow Trout

Sepahi

Tacchi

Casadei

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

Chemokines and chemokine receptors rapidly diversified in teleost fish but their immune functions remain unclear. We report here that Chemokine (C-C motif) ligand 19 (CCL19), a chemokine known to control lymphocyte migration and compartmentalization of lymphoid tissues in mammals, diversified in salmonids leading to the presence of six CCL19-like genes named CK10a, CK10b, CK12a, CK12b, CK13a and CK13b. Salmonid CCL19-like genes all contain the DCCL conserved motif but share low amino acid sequence identity. CK12 (but not CK10 or CK13) is constitutively expressed at high levels in all four trout MALT. Nasal vaccination with a live attenuated virus results in sustained up-regulation of CK12 (but not CK10 or CK13) expression in trout NALT. Trout recombinant CK12a (rCK12a) is not chemotactic in vitro but it increases the width of the nasal lamina propria (LP) when delivered intranasally (I.N.). rCK12a delivered I.N or i.p. stimulates the expression of CD8α, granulysin, and IFNγ in mucosal and systemic compartments and increases nasal CD8α+ cell numbers. rCK12a is able to stimulate proliferation of head kidney leucocytes (HKLs) from antigen experienced trout but not naïve controls yet it does not confer protection against viral challenge. These results show that local nasal production of CK12a contributes to antiviral immune protection both locally and systemically via stimulation of CD8 cellular immune responses and highlights a conserved role for CK12 in the orchestration of mucosal and systemic immune responses against viral pathogens in vertebrates.

show abstract

“…Different sulfation patterns affect the selectivity of synthetic N-terminal peptides from CCR3 for CCL11/eotaxin-1, CCL24/eotaxin-2, and CCL26/eotaxin-3 and are hypothesized to contribute to ligand biased signaling in intact CCR3 (Zhu et al, 2011). Unlike CCR3 or CCR7, which have multiple and in most cases monomeric ligands (Love, Sandberg, Ziarek, Gerarden et al, 2012; Millard et al, 2014; Veldkamp et al, 2015), CXCR4 has only one natural ligand CXCL12. Peptides and sulfopeptides corresponding to the N-terminus of CXCR4 promote CXCL12 dimer formation and a covalently locked CXCL12 dimer with a nearly identical structure to the wild-type CXCL12 dimer signals through CXCR4 as a partial agonist (Drury, Ziarek, Gravel, Veldkamp et al, 2011; Veldkamp et al, 2008; Veldkamp et al, 2006; Ziarek et al, 2013).…”

Section: Perspectivesmentioning

confidence: 99%

“…Resting T-cells expressing PSGL-1 show enhanced chemotaxis towards the homeostatic chemokines CCL19 and CCL21 and increased recruitment to secondary lymphoid organs (Veerman, Williams, Uchimura, Singer et al, 2007). However, these enhancements are not a result of the canonical PSGL-1 selectin interactions, but result form the N-terminus of PSGL-1 binding directly to CCL19 or CCL21 (Veerman et al, 2007; Veldkamp, Kiermaier, Gabel-Eissens, Gillitzer et al, 2015). It is not surprising that the acidic, sulfotyrosine containing N-terminus of PSGL-1 binds CCL19 or CCL21.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Analysis of N-Terminal Chemokine Receptor Sulfopeptides Using Tyrosylprotein Sulfotransferase Enzymes

Seibert

Sanfiz

Sakmar

et al. 2016

Methods in Enzymology

Self Cite

View full text Add to dashboard Cite

In most chemokine receptors, one or multiple tyrosine residues have been identified within the receptor N-terminal domain that are, at least partially, modified by post-translational tyrosine sulfation. For example, tyrosine sulfation has been demonstrated for Tyr-3, -10, -14, and -15 of CCR5, for Tyr-3, -14, and -15 of CCR8 and for Tyr-7, -12, and -21 of CXCR4. While there is evidence for several chemokine receptors that tyrosine sulfation is required for optimal interaction with the chemokine ligands, the precise role of tyrosine sulfation for chemokine receptor function remains unclear. Furthermore, the function of the chemokine receptor N-terminal domain in chemokine binding and receptor activation is also not well understood. Sulfotyrosine peptides corresponding to the chemokine receptor N-termini are valuable tools to address these important questions both in structural and functional studies. However, due to the liability of the sulfotyrosine modification, these peptides are difficult to obtain using standard peptide chemistry methods. In this chapter, we provide methods to prepare sulfotyrosine peptides by enzymatic in vitro sulfation of peptides using purified recombinant tyrosylprotein sulfotransferase (TPST) enzymes. In addition, we also discuss alternative approaches for the generation of sulfotyrosine peptides and methods from sulfopeptide analysis.

show abstract

Solution Structure of CCL19 and Identification of Overlapping CCR7 and PSGL-1 Binding Sites

Cited by 36 publications

References 23 publications

Transferring the C-terminus of the chemokine CCL21 to CCL19 confers enhanced heparin binding

Transferring the C-terminus of the chemokine CCL21 to CCL19 confers enhanced heparin binding

CK12a, a CCL19-like Chemokine That Orchestrates both Nasal and Systemic Antiviral Immune Responses in Rainbow Trout

Preparation and Analysis of N-Terminal Chemokine Receptor Sulfopeptides Using Tyrosylprotein Sulfotransferase Enzymes

Contact Info

Product

Resources

About