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Structural and functional characterization of CC chemokine CCL14.

Structural and functional characterization of CC chemokine CCL14. Research Abstract Details 

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  • Structural and functional characterization of CC chemokine CCL14. Abstract Text:

    katherine y blainKatherine Y Blain,witek kwiatkowskiWitek Kwiatkowski,qinghai zhaoQinghai Zhao,david la fleurDavid La Fleur,chethana naikChethana Naik,tae-wook chunTae-Wook Chun,tatiana tsarevaTatiana Tsareva,palanisamy kanakarajPalanisamy Kanakaraj,michael w lairdMichael W Laird,rutul shahRutul Shah,lisa georgeLisa George,indra sanyalIndra Sanyal,paul a moorePaul A Moore,borries demelerBorries Demeler,senyon choeSenyon Choe,

    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 microM 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.

    Structural and functional characterization of CC chemokine CCL14. Publishing Authors By Initials

    ky blainKY Blain,w kwiatkowskiW Kwiatkowski,q zhaoQ Zhao,d la fleurD La Fleur,c naikC Naik,tw chunTW Chun,t tsarevaT Tsareva,p kanakarajP Kanakaraj,mw lairdMW Laird,r shahR Shah,l georgeL George,i sanyalI Sanyal,pa moorePA Moore,b demelerB Demeler,s choeS Choe,

    For similar biological phenomena, cell phenomena, and immunity: biological phenomena: microbiologic phenomena: viral physiology: virus internalization research abstracts see: biological phenomena, cell phenomena, and immunity: biological phenomena: microbiologic phenomena: viral physiology: virus internalization research

    PUBMED ID PMID:

    MEDLINE DATE:

    Structural and functional characterization of CC chemokine CCL14. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: Biochemistry

    VOLUME: 46

    Page Numbers: 10008-15

    Journal Abbreviation: Biochemistry

    ISSN: 0006-2960

    DAY: 11

    MONTH: 08

    YEAR: 2007

    Structural and functional characterization of CC chemokine CCL14. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 370623

    Structural and functional characterization of CC chemokine CCL14. Keywords Mesh Terms:

    KEYWORDS: Virus Internalization

    MESH TERMS: drug effects

    Chemical & Substance for Abstract: Structural and functional characterization of CC chemokine CCL14. Information

    Substance Name: Endopeptidases

    Registry Number: EC 3.4.-

    Grant and Affiliation Information for Structural and functional characterization of CC chemokine CCL14.

    AFFILIATION: Structural Biology Laboratory, The Salk Institute, La Jolla, California 92037, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States PHS

    GRANT: RRR022200

    ACRONYM: HD

    MEDLINETA: Biochemistry

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER: 2Q8T

    Number Hits: 0

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