2M74

1H, 13C and 15N assignments of the four N-terminal domains of human fibrillin-1

Summary for 2M74

• Entry DOI: 10.2210/pdb2m74/pdb
• NMR Information: BMRB: 18843
• Descriptor: Fibrillin-1 (1 entity in total)
• Functional Keywords: structural protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix: P35555
• Total number of polymer chains: 1
• Total formula weight: 14120.08

Authors

Yadin, D.A.,Robertson, I.B.,Jensen, S.A.,Handford, P.A.,Redfield, C. (deposition date: 2013-04-17, release date: 2013-09-25, Last modification date: 2024-10-30)

Primary citation

Yadin, D.A.,Robertson, I.B.,McNaught-Davis, J.,Evans, P.,Stoddart, D.,Handford, P.A.,Jensen, S.A.,Redfield, C.
Structure of the Fibrillin-1 N-Terminal Domains Suggests that Heparan Sulfate Regulates the Early Stages of Microfibril Assembly.
Structure, 21:1743-1756, 2013

PubMed 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.

PubMed: 24035709
DOI: 10.1016/j.str.2013.08.004

Experimental method

SOLUTION NMR