Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Submit a comment

Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity
Jonathan Lam, … , Steven L. Teitelbaum, Daved H. Fremont
Jonathan Lam, … , Steven L. Teitelbaum, Daved H. Fremont
Published October 1, 2001
Citation Information: J Clin Invest. 2001;108(7):971-979. https://doi.org/10.1172/JCI13890.
View: Text | PDF
Article

Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity

  • Text
  • PDF
Abstract

RANK, the receptor activator of NF-κB, and its ligand RANKL (initially termed TRANCE, also termed ODF and OPGL), are a TNF superfamily receptor-ligand pair that govern the development and function of osteoclasts, lymphoid tissue, and mammary epithelium. While TNF family cytokines share a common structural scaffold, individual receptor-ligand pairs associate with high specificity. Given the low level of amino acid conservation among members of the TNF superfamily, the means by which these molecules achieve specificity cannot be completely understood without knowledge of their three-dimensional structures. To determine the elements of RANKL that mediate RANK activation, we have crystallized the ectodomain of murine RANKL and solved its structure to a resolution of 2.6 Å. RANKL self-associates as a homotrimer with four unique surface loops that distinguish it from other TNF family cytokines. Mutagenesis of selected residues in these loops significantly modulates RANK activation, as evidenced by in vitro osteoclastogenesis, thereby establishing their necessity in mediating the biological activities of RANKL. Such structural determinants of RANKL-RANK specificity may be of relevance in the pharmacologic design of compounds to ameliorate osteopenic disorders of bone.

Authors

Jonathan Lam, Christopher A. Nelson, F. Patrick Ross, Steven L. Teitelbaum, Daved H. Fremont

×

Guidelines

The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.

  • Comments appear on the Journal’s website and are linked from the original article’s web page.
  • Authors are notified by email if their comments are posted.
  • The Journal reserves the right to edit comments for length and clarity.
  • No appeals will be considered.
  • Comments are not indexed in PubMed.

Specific requirements

  • Maximum length, 400 words
  • Entered as plain text or HTML
  • Author’s name and email address, to be posted with the comment
  • Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
  • Comments may not include figures
This field is required
This field is required
This field is required
This field is required
This field is required
This field is required
Rich Text Editor, eletter_body
Editor toolbarsClipboard/Undo CutKeyboard shortcut Ctrl+X CopyKeyboard shortcut Ctrl+C PasteKeyboard shortcut Ctrl+V Paste as plain textKeyboard shortcut Ctrl+Alt+Shift+V Paste from Word UndoKeyboard shortcut Ctrl+Z RedoKeyboard shortcut Ctrl+YEditing Find Replace Select All Spell Check As You TypeLinks LinkKeyboard shortcut Ctrl+K Unlink AnchorForms Form Checkbox Radio Button Text Field Textarea Selection Field Button Image Button Hidden FieldTools Maximize Show BlocksDocument Source Save New Page Preview Print TemplatesBasic Styles BoldKeyboard shortcut Ctrl+B ItalicKeyboard shortcut Ctrl+I UnderlineKeyboard shortcut Ctrl+U Strikethrough Subscript Superscript Copy FormattingKeyboard shortcut Ctrl+Shift+C Remove FormatParagraph Insert/Remove Numbered List Insert/Remove Bulleted List Decrease Indent Increase Indent Block Quote Create Div Container Align Left Center Align Right Justify Text direction from left to right Text direction from right to left Set languageStylesStylesStylesFormatFormatFontFontSizeSizeColors Text Color Background Color
Press ALT 0 for help
◢Elements path 

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts