PDBsum entry 2w86

Glycoprotein

PDB id: 2w86

Contents

Protein chain

147 a.a. *

Metals

IOD ×3

_CA ×2

Waters ×148

* Residue conservation analysis

PDB id:

2w86

Name:

Glycoprotein

Title:

Crystal structure of fibrillin-1 domains cbegf9hyb2cbegf10, calcium saturated form

Structure:

Fibrillin-1. Chain: a. Fragment: cbegf9hyb2cbegf10, residues 807-951. Synonym: fibrillin1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

1.80Å R-factor: 0.187 R-free: 0.221

Authors:

S.A.Jensen,S.Iqbal,E.D.Lowe,C.Redfield,P.A.Handford

Key ref:

S.A.Jensen et al. (2009). Structure and Interdomain Interactions of a Hybrid Domain: A Disulphide-Rich Module of the Fibrillin/LTBP Superfamily of Matrix Proteins. Structure, 17, 759-768. PubMed id: 19446531 DOI: 10.1016/j.str.2009.03.014

Date:

09-Jan-09 Release date: 26-May-09

Protein chain

P35555  (FBN1_HUMAN) -  Fibrillin-1 from Homo sapiens

Seq: 2871 a.a.

Struc: 147 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.str.2009.03.014

Structure 17:759-768 (2009)

PubMed id: 19446531

Structure and Interdomain Interactions of a Hybrid Domain: A Disulphide-Rich Module of the Fibrillin/LTBP Superfamily of Matrix Proteins.

S.A.Jensen, S.Iqbal, E.D.Lowe, C.Redfield, P.A.Handford.

ABSTRACT

The fibrillins and latent transforming growth factor-beta binding proteins (LTBPs) form a superfamily of structurally-related proteins consisting of calcium-binding epidermal growth factor-like (cbEGF) domains interspersed with 8-cysteine-containing transforming growth factor beta-binding protein-like (TB) and hybrid (hyb) domains. Fibrillins are the major components of the extracellular 10-12 nm diameter microfibrils, which mediate a variety of cell-matrix interactions. Here we present the crystal structure of a fibrillin-1 cbEGF9-hyb2-cbEGF10 fragment, solved to 1.8 A resolution. The hybrid domain fold is similar, but not identical, to the TB domain fold seen in previous fibrillin-1 and LTBP-1 fragments. Pairwise interactions with neighboring cbEGF domains demonstrate extensive interfaces, with the hyb2-cbEGF10 interface dependent on Ca(2+) binding. These observations provide accurate constraints for models of fibrillin organization within the 10-12 nm microfibrils and provide further molecular insights into how Ca(2+) binding influences the intermolecular interactions and biomechanical properties of fibrillin-1.

Selected figure(s)

Figure 1.
Figure 1. Domain Organization of Human Fibrillin-1
The fibrillin sequence is largely dominated by cbEGF domains, interspersed with TB and hyb domains. Constructs used to determine Ca^2+ affinities of hyb-cbEGF pairs and the cbEGF9-hyb2-cbEGF10 construct are shown above the figure.

Figure 4.
Figure 4. Residues Involved in the Formation of Interdomain Interfaces
(A and B) Residues involved in interdomain contacts were identified using the program Contact in the CCP4 program suite (CCP4, 1994), with a distance limit of 4 Å. Hyb domain residues at the cbEGF9-hyb2 interface (A) or hyb2-cbEGF10 interface (B) are indicated by magenta spheres and interacting cbEGF residues are indicated by green spheres.
(C) An alignment of the hyb2 and TB4 domains shows similarities of the regions involved in interactions with either the N-terminal (red) or C-terminal (cyan) cbEGFs. Domains were aligned using Clustal W 2.0 (Larkin et al., 2007), and cysteines are highlighted in yellow.

The above figures are reprinted from an Open Access publication published by Cell Press: Structure (2009, 17, 759-768) copyright 2009.

Figures were selected by an automated process.