Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Molecular Architecture of the Bardet-Biedl Syndrome Protein 2-7-9 Subcomplex

View ORCID ProfileW. Grant Ludlam, Takuma Aoba, Jorge Cuéllar, M. Teresa Bueno-Carrasco, Aman Makaju, James D. Moody, Sarah Franklin, José M. Valpuesta, Barry M. Willardson
doi: https://doi.org/10.1101/699223
W. Grant Ludlam
1Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for W. Grant Ludlam
Takuma Aoba
1Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jorge Cuéllar
2Centro Nacional de Biotecnología (CNB-CSIC), Campus de la Universidad Autónoma de Madrid, 28049 Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Teresa Bueno-Carrasco
2Centro Nacional de Biotecnología (CNB-CSIC), Campus de la Universidad Autónoma de Madrid, 28049 Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aman Makaju
3Department of Internal Medicine, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James D. Moody
1Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarah Franklin
3Department of Internal Medicine, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
José M. Valpuesta
2Centro Nacional de Biotecnología (CNB-CSIC), Campus de la Universidad Autónoma de Madrid, 28049 Madrid, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: bmwillardson@chem.byu.edu jmv@cnb.csic.es
Barry M. Willardson
1Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: bmwillardson@chem.byu.edu jmv@cnb.csic.es
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Summary

Bardet-Biedl syndrome (BBS) is a genetic disease caused by mutations that disrupt the function of the BBSome, an eight-subunit complex that plays an important role in transport of proteins in primary cilia. To better understand the molecular basis of the disease, we analyzed the structure of a BBSome subcomplex consisting of three homologous BBS proteins (BBS2, BBS7, and BBS9) by an integrative structural modeling approach using electron microscopy and chemical crosslinking coupled with mass spectrometry. The resulting molecular model revealed an overall structure that resembles a flattened triangle. Within the structure, BBS2 and BBS7 form a tight dimer based on a coiled-coil interaction, and BBS9 associates with the dimer via an interaction with the α-helical domain of BBS2. Interestingly, a BBS-linked mutation of BBS2 (R632P) is located in the α-helical domain at the interface between BBS2 and BBS9, and binding experiments showed that this mutation disrupted the interaction of BBS2 with BBS9. This finding suggests that BBSome assembly is disrupted by the R632P substitution, providing a molecular explanation for BBS in patients harboring this mutation.

Footnotes

  • Abbreviations: BBS, Bardet-Biedl Syndrome; BBSome, BBS protein ciliary transport complex; BBS2-7-9, BBSome subcomplex containing BBS2, 7 and 9 proteins; IFT, intraflagellar transport; ARL6, ADP-ribosylation factor-like protein 6; LZTFL1, Leucine zipper transcription factor-like protein 1; CCT, cytosolic chaperonin containing tailless polypeptide 1; EM, electron microscopy; XL-MS, chemical crosslinking coupled with mass spectrometry; HEK-293T, human embryonic kidney 293T cells; DMEM, Dulbecco modified eagle media; FBS, fetal bovine serum; HPC4, protein C peptide tag; PEI, polyethylenimine; LC, liquid chromatography; MS/MS, tandem mass spectrometry; DSS, disuccinimidyl suberate; DSG, disuccinimidyl glutarate; IMP, integrative modeling platform; GAE, γ-adaptin ear domain; RMSD, root mean square deviation.

  • ftp://MSV000081472@massive.ucsd.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted July 11, 2019.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Molecular Architecture of the Bardet-Biedl Syndrome Protein 2-7-9 Subcomplex
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Molecular Architecture of the Bardet-Biedl Syndrome Protein 2-7-9 Subcomplex
W. Grant Ludlam, Takuma Aoba, Jorge Cuéllar, M. Teresa Bueno-Carrasco, Aman Makaju, James D. Moody, Sarah Franklin, José M. Valpuesta, Barry M. Willardson
bioRxiv 699223; doi: https://doi.org/10.1101/699223
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Molecular Architecture of the Bardet-Biedl Syndrome Protein 2-7-9 Subcomplex
W. Grant Ludlam, Takuma Aoba, Jorge Cuéllar, M. Teresa Bueno-Carrasco, Aman Makaju, James D. Moody, Sarah Franklin, José M. Valpuesta, Barry M. Willardson
bioRxiv 699223; doi: https://doi.org/10.1101/699223

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biochemistry
Subject Areas
All Articles
  • Animal Behavior and Cognition (4383)
  • Biochemistry (9599)
  • Bioengineering (7092)
  • Bioinformatics (24863)
  • Biophysics (12615)
  • Cancer Biology (9957)
  • Cell Biology (14354)
  • Clinical Trials (138)
  • Developmental Biology (7948)
  • Ecology (12107)
  • Epidemiology (2067)
  • Evolutionary Biology (15989)
  • Genetics (10925)
  • Genomics (14742)
  • Immunology (9869)
  • Microbiology (23675)
  • Molecular Biology (9485)
  • Neuroscience (50868)
  • Paleontology (369)
  • Pathology (1539)
  • Pharmacology and Toxicology (2683)
  • Physiology (4015)
  • Plant Biology (8657)
  • Scientific Communication and Education (1508)
  • Synthetic Biology (2397)
  • Systems Biology (6436)
  • Zoology (1346)