Structure of the Fibrillin-1 N-Terminal Domains Suggests that Heparan Sulfate Regulates the Early Stages of Microfibril Assembly
Yadin, David A., Robertson, Ian B., McNaught-Davis, Joanne, Evans, Paul, Stoddart, David, Handford, Penny A., Jensen, Sacha A., and Redfield, Christina (2013) Structure of the Fibrillin-1 N-Terminal Domains Suggests that Heparan Sulfate Regulates the Early Stages of Microfibril Assembly. Structure, 21 (10). pp. 1743-1756.
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Abstract
The human extracellular matrix glycoprotein fibrillin-1 is the primary component of the 10- to 12-nm-diameter microfibrils, which perform key structural and regulatory roles in connective tissues. Relatively little is known about the molecular mechanisms of fibrillin assembly into microfibrils. Studies using recombinant fibrillin fragments indicate that an interaction between the N- and C-terminal regions drives head-to-tail assembly. Here, we present the structure of a fibrillin N-terminal fragment comprising the fibrillin unique N-terminal (FUN) and the first three epidermal growth factor (EGF)-like domains (FUN-EGF3). Two rod-like domain pairs are separated by a short, flexible linker between the EGF1 and EGF2 domains. We also show that the binding site for the C-terminal region spans multiple domains and overlaps with a heparin interaction site. These data suggest that heparan sulfate may sequester fibrillin at the cell surface via FUN-EGF3 prior to aggregation of the C terminus, thereby regulating microfibril assembly.
| Item ID: | 60804 |
|---|---|
| Item Type: | Article (Research - C1) |
| ISSN: | 1878-4186 |
| Copyright Information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Date Deposited: | 17 Jul 2024 01:52 |
| FoR Codes: | 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060112 Structural Biology (incl Macromolecular Modelling) @ 75% 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060199 Biochemistry and Cell Biology not elsewhere classified @ 25% |
| SEO Codes: | 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100% |
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