PDBsum entry 1oww

Structural protein

PDB id: 1oww

Contents

Protein chain

93 a.a. *

* Residue conservation analysis

PDB id:

1oww

Name:

Structural protein

Title:

Solution structure of the first type iii module of human fibronectin determined by 1h, 15n nmr spectroscopy

Structure:

Fibronectin first type iii module. Chain: a. Fragment: residues 608-701 of sws p02751. Synonym: fn. Cold-insoluble globulin. Cig. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fn1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

NMR struc:

24 models

Authors:

M.Gao,D.Craig,O.Lequin,I.D.Campbell,V.Vogel,K.Schulten

Key ref:

M.Gao et al. (2003). Structure and functional significance of mechanically unfolded fibronectin type III1 intermediates. Proc Natl Acad Sci U S A, 100, 14784-14789. PubMed id: 14657397 DOI: 10.1073/pnas.2334390100

Date:

31-Mar-03 Release date: 07-Oct-03

Protein chain

P02751  (FINC_HUMAN) -  Fibronectin from Homo sapiens

Seq: 2477 a.a.

Struc: 93 a.a.

DOI no: 10.1073/pnas.2334390100

Proc Natl Acad Sci U S A 100:14784-14789 (2003)

PubMed id: 14657397

Structure and functional significance of mechanically unfolded fibronectin type III1 intermediates.

M.Gao, D.Craig, O.Lequin, I.D.Campbell, V.Vogel, K.Schulten.

ABSTRACT

Fibronectin (FN) forms fibrillar networks coupling cells to the extracellular matrix. The formation of FN fibrils, fibrillogenesis, is a tightly regulated process involving the exposure of cryptic binding sites in individual FN type III (FN-III) repeats presumably exposed by mechanical tension. The FN-III1 module has been previously proposed to contain such cryptic sites that promote the assembly of extracellular matrix FN fibrils. We have combined NMR and steered molecular dynamics simulations to study the structure and mechanical unfolding pathway of FN-III1. This study finds that FN-III1 consists of a beta-sandwich structure that unfolds to a mechanically stable intermediate about four times the length of the native folded state. Considering previous experimental findings, our studies provide a structural model by which mechanical stretching of FN-III1 may induce fibrillogenesis through this partially unfolded intermediate.

Selected figure(s)

Figure 2.
Fig. 2. Structures of equilibrated FN-III[1]. (a) Alignment of NMR (cyan) and equilibrated (pink) structures shown in two different orientations. Two prolines that prevent A and B strands forming more interstrand hydrogen bonds are colored purple. Interstrand hydrogen bond networks of the ABE (b) and of the GFCD -sheets (c), the latter in different orientations. Hydrogen and oxygen atoms are colored white and orange. Hydrogen bonds are represented by black dashed lines.

Figure 3.
Fig. 3. Mechanical unfolding intermediates of FN-III[1]. Curves shown (Top Left) are force vs. distance R[NC] profiles from constant velocity SMD unfolding simulations of FN-III[1] at speeds of 0.05 and 0.01 Å/ps. R[NC] is defined as the end-to-end distance between two termini. Multiple runs at the same velocity are differentiated by a numeric suffix. Two force peak regions separated 95 Å are highlighted. Four unfolding intermediates (I[1]-I[4]) characterizing the unfolding pathway of FN-III[1] are shown as snapshots in cartoon representation. Transition from aligned state I[2] to I[3] and from I[3] to I[4] requires disrupting certain interstrand hydrogen bonds between two -sheets, ABE (a) and GFCD (b and c). The disruptions need assistance from surrounding water molecules (purple) that attack hydrogen bonds. Formed hydrogen bonds between backbone oxygen (orange) and hydrogen (white) atoms are represented as thick black lines.

Figures were selected by the author.