PDBsum entry 1fnh

Heparin and integrin binding

PDB id: 1fnh

Contents

Protein chain

269 a.a. *

Waters ×241

* Residue conservation analysis

PDB id:

1fnh

Name:

Heparin and integrin binding

Title:

Crystal structure of heparin and integrin binding segment of human fibronectin

Structure:

Protein (fibronectin). Chain: a. Fragment: heparin and integrin binding. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Tetramer (from PQS)

Resolution:

2.80Å R-factor: 0.216 R-free: 0.295

Authors:

A.Sharma,J.Askari,M.Humphries,E.Y.Jones,D.I.Stuart

Key ref:

A.Sharma et al. (1999). Crystal structure of a heparin- and integrin-binding segment of human fibronectin. EMBO J, 18, 1468-1479. PubMed id: 10075919 DOI: 10.1093/emboj/18.6.1468

Date:

28-Jan-99 Release date: 16-Mar-99

Protein chain

P02751  (FINC_HUMAN) -  Fibronectin from Homo sapiens

Seq: 2477 a.a.

Struc: 269 a.a.

DOI no: 10.1093/emboj/18.6.1468

EMBO J 18:1468-1479 (1999)

PubMed id: 10075919

Crystal structure of a heparin- and integrin-binding segment of human fibronectin.

A.Sharma, J.A.Askari, M.J.Humphries, E.Y.Jones, D.I.Stuart.

ABSTRACT

The crystal structure of human fibronectin (FN) type III repeats 12-14 reveals the primary heparin-binding site, a clump of positively charged residues in FN13, and a putative minor site approximately 60 A away in FN14. The IDAPS motif implicated in integrin alpha4beta1 binding is at the FN13-14 junction, rendering the critical Asp184 inaccessible to integrin. Asp184 clamps the BC loop of FN14, whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9. Mutagenesis studies prompted by this observation reveal that both arginines of the PRARI sequence are important for alpha4beta1 binding to FN12-14. The PRARI motif may represent a new class of integrin-binding sites. The spatial organization of the binding sites suggests that heparin and integrin may bind in concert.

Selected figure(s)

Figure 1.
Figure 1 (A) The modular architecture of human FN showing the type I, II and III repeats and the known binding sites for various ligands. Boxes in green and blue correspond to regions where structural information is available (Williams et al., 1994; Leahy et al., 1996; Sticht et al., 1998). (B) A structure-based sequence alignment of 17 type III human FN repeats. Secondary structure classification is based on all repeats in FN12–14; FNEDA and FNEDB denotes the extra repeats A and B. Residues in green are identical in all 17 repeats, in aquamarine are identical in at least 12 repeats, and in yellow identical in 8–11 repeats. Residues in red are implicated in integrin binding. The first nine residues of FN15 (shaded) are part of IIICS (see text). All molecular graphic figures are generated using BOBSCRIPT (Esnouf, 1997) and RASTER3D (Merritt and Murphy, 1994), or GRASP (Nicholls et al., 1991).

Figure 2.
Figure 2 Orthogonal views of FN12–14 structure. The structure is represented as a cartoon with the -strands (defined by inspection) shown as arrows. The chain is coloured from blue to green to red as the polypeptide goes from the N- to the C-terminus. The repeats correspond to FN12, FN13 and FN14. Individual strands are labelled in one repeat in each case.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 1468-1479) copyright 1999.

Figures were selected by an automated process.