PDBsum entry 1uzp

Matrix protein

PDB id: 1uzp

Contents

Protein chain

152 a.a. *

Metals

_SM ×3

Waters ×188

* Residue conservation analysis

PDB id:

1uzp

Name:

Matrix protein

Title:

Integrin binding cbegf22-tb4-cbegf33 fragment of human fibrillin-1, sm bound form cbegf23 domain only.

Structure:

Fibrillin-1. Chain: a. Fragment: begf22-tb4-cbegf23, residues 1486-1647. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: extra-ellular matrix. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.78Å R-factor: 0.210 R-free: 0.254

Authors:

S.S.J.Lee,V.Knott,K.Harlos,P.A.Handford,D.I.Stuart

Key ref:

S.S.Lee et al. (2004). Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization. Structure, 12, 717-729. PubMed id: 15062093 DOI: 10.1016/j.str.2004.02.023

Date:

15-Mar-04 Release date: 08-Apr-04

Protein chain

P35555  (FBN1_HUMAN) -  Fibrillin-1 from Homo sapiens

Seq: 2871 a.a.

Struc: 152 a.a.

DOI no: 10.1016/j.str.2004.02.023

Structure 12:717-729 (2004)

PubMed id: 15062093

Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization.

S.S.Lee, V.Knott, J.Jovanović, K.Harlos, J.M.Grimes, L.Choulier, H.J.Mardon, D.I.Stuart, P.A.Handford.

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.

Selected figure(s)

Figure 6.
Figure 6. Models of Fibrillin-1 and Microfibril Organization(A) Homology model for cbEGF11-TB5. cbEGF and TB domains are colored green and blue, respectively. The crystal structure of cbEGF22-TB4-cbEGF23 fragment is highlighted in bold. Ca^2+ and potential N-linked glycosylation sites are represented by red and black spheres, respectively. The RGD motif on the TB4 loop is indicated.(B) A simple model of the fibrillin microfibril. The arrows represent fibrillin-1 molecules with dimensions based on the knowledge of the component domains. The intermolecular transglutaminase cross-links are shown as X and the associated protein MAGP-1 as a turquoise diamond. A sketch of the STEM data of Baldock et al. (2001) is shown below. The colored regions mark the sites of known antibody epitopes (red, 2502; green, 11C1.3; purple, PF2; yellow, 2499). The bead regions are shown as gray ellipses.

The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 717-729) copyright 2004.

Figure was selected by the author.