Structural insights into the mechanical regulation of molecular recognition sites

• Published in: Trends in biotechnology (Regular ed.) 2001-10, Vol.19 (10), p.416-423
• Main Authors: Vogel, Viola, Thomas, Wendy E, Craig, David W, Krammer, André, Baneyx, Gretchen
• Format: Article
• Language: English
• Subjects: atomic force microscopy; Binding Sites - physiology; Biological and medical sciences; Biotechnology; Cell membranes; Cell physiology; cryptic sites; extracellular matrix; fibronectin; Fibronectins - chemistry; Fibronectins - metabolism; Fundamental and applied biological sciences. Psychology; integrin; integrins; Integrins - chemistry; Integrins - metabolism; Molecular and cellular biology; Molecular structure; monolayer experiments; protein function; recognition sites; RGD loop; Signal transduction; Signal Transduction - physiology; steered molecular dynamics; Structure-Activity Relationship
• ISSN: 0167-7799; 1879-3096
• DOI: 10.1016/S0167-7799(01)01737-1

Intriguing experimental and computational data are emerging to suggest that mechanical forces regulate the functional states of some proteins by stretching them into nonequilibrium states. Using the extracellular matrix protein fibronectin as an example, we discuss molecular design principles that might control the exposure of a protein's recognition sites, and/or their relative distances, in a force-dependent manner. Fibronectin regulates many cellular functions by binding directly to integrins. Although integrins have a key role in the transduction of force across the cell membrane by coupling the extracellular matrix to the cytoskeleton, the studies reviewed here suggest that fibronectin might be one of the molecules responsible for the initial transformation of mechanical force into a biochemical signal.