Selectivity and antagonism of chemokine receptors (original) (raw)

Journal Article

,

Glaxo Institute for Molecular Biology

,

Geneva

,

Switzerland

Reprint requests: Timothy N.C. Wells, Glaxo Institute for Molecular Biology, 14 chemin des Aulx, 1228 Plan-les-Ouates, Geneva, Switzerland.

Search for other works by this author on:

,

Glaxo Institute for Molecular Biology

,

Geneva

,

Switzerland

Search for other works by this author on:

,

Glaxo Institute for Molecular Biology

,

Geneva

,

Switzerland

Search for other works by this author on:

,

Glaxo Institute for Molecular Biology

,

Geneva

,

Switzerland

Search for other works by this author on:

,

Glaxo Wellcome Medicines Research Centre

,

Stevenage

,

United Kingdom

Search for other works by this author on:

,

Glaxo Wellcome Medicines Research Centre

,

Stevenage

,

United Kingdom

Search for other works by this author on:

,

Glaxo Institute for Molecular Biology

,

Geneva

,

Switzerland

Search for other works by this author on:

Glaxo Institute for Molecular Biology

,

Geneva

,

Switzerland

Search for other works by this author on:

Accepted:

29 September 1995

Published:

01 January 1996

Cite

Timothy N C Wells, Christine A Power, Manjula Lusti-Narasimhan, Arlene J Hoogewerf, Robert M Cooke, Chun-wa Chung, Manuel C Peitsch, Amanda E I Proudfoot, Selectivity and antagonism of chemokine receptors, Journal of Leukocyte Biology, Volume 59, Issue 1, January 1996, Pages 53–60, https://doi.org/10.1002/jlb.59.1.53
Close

Navbar Search Filter Mobile Enter search term Search

Abstract

The chemokine superfamily can be sub-divided into two groups based on their amino terminal cysteine spacing. The CXC chemokines are primarily involved in neutrophil-mediated inflammation and, so far, two human receptors have been cloned. The CC chemokines tend to be involved in chronic inflammation, and recently we have cloned a fourth leukocyte receptor for this group of ligands. Understanding what makes one receptor bind its range of agonists is important if we are to develop potent selective antagonists. We have started to investigate the molecular basis of this receptor selectivity by looking at why CC chemokines do not bind to the CXC receptors in several ways. First, we looked at the role of the three-dimensional structure of the ligand, and have solved the three-dimensional structure of RANTES using nuclear magnetic resonance spectroscopy. The structure is similar to that already determined for the CC chemokine macrophage inflammatory protein-1β, and it has a completely different dimer interface to that of the CXC chemokine interleukin-8 (IL-8). However, the monomer structures of all the chemokines are very similar, and at physiological concentrations the proteins are likely to be monomeric. Second, by examining all the known CC and CXC chemokines, we have found a region that differs between the two subfamilies. Mutations of one of the residues in this region, Leu-25 in IL-8, to tyrosine (which is conserved at this position in CC chemokines) enables the mutant IL-8 to bind CC-chemokine receptor-1 (CC-CKR-1) and introduces monocyte chemoattractant activity. Using other mutations in this region, we can show a direct interaction with the N-terminus of CC-CKR-1. Third, we have found that modification of the amino terminus of RANTES by addition of one amino acid makes it into an antagonist with nanomolar potency. Taken together, this data suggests a two-site model for receptor activation and for selectivity between CC and CXC chemokines, with an initial receptor contact provided by the main body of the chemokine, and activation provided by the amino terminal region.

This content is only available as a PDF.

© 1996 Society for Leukocyte Biology

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)

You do not currently have access to this article.

Personal account

Get help with access

Institutional access

Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:

IP based access

Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account.

Sign in through your institution

Choose this option to get remote access when outside your institution. Shibboleth/Open Athens technology is used to provide single sign-on between your institution’s website and Oxford Academic.

  1. Click Sign in through your institution.
  2. Select your institution from the list provided, which will take you to your institution's website to sign in.
  3. When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account.
  4. Following successful sign in, you will be returned to Oxford Academic.

If your institution is not listed or you cannot sign in to your institution’s website, please contact your librarian or administrator.

Sign in with a library card

Enter your library card number to sign in. If you cannot sign in, please contact your librarian.

Society Members

Society member access to a journal is achieved in one of the following ways:

Sign in through society site

Many societies offer single sign-on between the society website and Oxford Academic. If you see ‘Sign in through society site’ in the sign in pane within a journal:

  1. Click Sign in through society site.
  2. When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.
  3. Following successful sign in, you will be returned to Oxford Academic.

If you do not have a society account or have forgotten your username or password, please contact your society.

Sign in using a personal account

Some societies use Oxford Academic personal accounts to provide access to their members. See below.

Personal account

A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.

Some societies use Oxford Academic personal accounts to provide access to their members.

Viewing your signed in accounts

Click the account icon in the top right to:

Signed in but can't access content

Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.

Institutional account management

For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.

Purchase

Short-term Access

To purchase short-term access, please sign in to your personal account above.

Don't already have a personal account? Register

Selectivity and antagonism of chemokine receptors - 24 Hours access

EUR €48.00

GBP £41.00

USD $51.00

Rental

Read this now at DeepDyve

This article is also available for rental through DeepDyve.

Citations

Views

Altmetric

Metrics

Total Views 13

0 Pageviews

13 PDF Downloads

Since 2/1/2023

Month: Total Views:
February 2023 1
March 2023 2
July 2023 1
August 2023 1
September 2023 1
October 2023 1
December 2023 1
January 2024 2
April 2024 1
June 2024 1
September 2024 1

Citations

157 Web of Science

×

Email alerts

Citing articles via

More from Oxford Academic