1UZQ

Integrin binding cbEGF22-TB4-cbEGF33 fragment of human fibrillin-1, apo form cbEGF23 domain only.

Summary for 1UZQ

• Entry DOI: 10.2210/pdb1uzq/pdb
• Related: 1APJ 1EMN 1EMO 1LMJ 1UZJ 1UZK 1UZP
• Descriptor: FIBRILLIN-1 (2 entities in total)
• Functional Keywords: matrix protein, extra-cellular matrix, fibrillin-1, cbegf domain, tb domain matrix protein
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 17332.44

Authors

Lee, S.S.J.,Knott, V.,Harlos, K.,Handford, P.A.,Stuart, D.I. (deposition date: 2004-03-15, release date: 2004-04-08, Last modification date: 2024-05-01)

Primary citation

Lee, S.S.J.,Knott, V.,Jovanovi, J.,Harlos, K.,Grimes, J.,Choulier, L.,Mardon, H.,Stuart, D.I.,Handford, P.A.
Structure of the Integrin Binding Fragment from Fibrillin-1 Gives New Insights Into Microfibril Organization
Structure, 12:717-, 2004

PubMed Abstract: Human fibrillin-1, the major structural protein of extracellular matrix (ECM) 10-12 nm microfibrils, is dominated by 43 calcium binding epidermal growth factor-like (cbEGF) and 7 transforming growth factor beta binding protein-like (TB) domains. Crystal structures reveal the integrin binding cbEGF22-TB4-cbEGF23 fragment of human fibrillin-1 to be a Ca(2+)-rigidified tetragonal pyramid. We suggest that other cbEGF-TB pairs within the fibrillins may adopt a similar orientation to cbEGF22-TB4. In addition, we have located a flexible RGD integrin binding loop within TB4. Modeling, cell attachment and spreading assays, immunocytochemistry, and surface plasmon resonance indicate that cbEGF22 bound to TB4 is a requirement for integrin activation and provide insight into the molecular basis of the fibrillin-1 interaction with alphaVbeta3. In light of our data, we propose a novel model for the assembly of the fibrillin microfibril and a mechanism to explain its extensibility.

PubMed: 15062093
DOI: 10.1016/J.STR.2004.02.023

Experimental method

X-RAY DIFFRACTION (2.4 Å)