Structure and functional significance of mechanically unfolded fibronectin type III1 intermediates

被引:162
作者
Gao, M
Craig, D
Lequin, O
Campbell, ID
Vogel, V
Schulten, K [1 ]
机构
[1] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA
[2] Univ Illinois, Dept Phys, Urbana, IL 61801 USA
[3] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA
[4] Univ Paris 06, UMR 7613 CNRS, F-75252 Paris 05, France
[5] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
[6] Univ Oxford, Oxford Ctr Mol Sci, Oxford OX1 3QU, England
关键词
D O I
10.1073/pnas.2334390100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:14784 / 14789
页数:6
相关论文
共 40 条
[1]   Fibronectin extension and unfolding within cell matrix fibrils controlled by cytoskeletal tension [J].
Baneyx, G ;
Baugh, L ;
Vogel, V .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (08) :5139-5143
[2]   Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer [J].
Baneyx, G ;
Baugh, L ;
Vogel, V .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (25) :14464-14468
[3]   Self-assembly of fibronectin into fibrillar networks underneath dipalmitoyl phosphatidylcholine monolayers: Role of lipid matrix and tensile forces [J].
Baneyx, G ;
Vogel, V .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) :12518-12523
[4]   THE PROGRAM XEASY FOR COMPUTER-SUPPORTED NMR SPECTRAL-ANALYSIS OF BIOLOGICAL MACROMOLECULES [J].
BARTELS, C ;
XIA, TH ;
BILLETER, M ;
GUNTERT, P ;
WUTHRICH, K .
JOURNAL OF BIOMOLECULAR NMR, 1995, 6 (01) :1-10
[5]   Anastellin, an FN3 fragment with fibronectin polymerization activity, resembles amyloid fibril precursors [J].
Briknarová, K ;
Åkerman, ME ;
Hoyt, DW ;
Ruoslahti, E ;
Ely, KR .
JOURNAL OF MOLECULAR BIOLOGY, 2003, 332 (01) :205-215
[6]   Fibronectin fibrillogenesis involves the heparin II binding domain of fibronectin [J].
Bultmann, H ;
Santas, AJ ;
Peters, DMP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (05) :2601-2609
[7]   Comparison of the early stages of forced unfolding for fibronectin type III modules [J].
Craig, D ;
Krammer, A ;
Schulten, K ;
Vogel, V .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (10) :5590-5595
[8]  
CRAIG D, 2004, IN PRESS STRUCTURE C
[10]   Identifying unfolding intermediates of FN-III10 by steered molecular dynamics [J].
Gao, M ;
Craig, D ;
Vogel, V ;
Schulten, K .
JOURNAL OF MOLECULAR BIOLOGY, 2002, 323 (05) :939-950