Editing Protein folding (section)

=== Single-molecule force spectroscopy ===
Single molecule techniques such as optical tweezers and AFM have been used to understand protein folding mechanisms of isolated proteins as well as proteins with chaperones.<ref name="pmid24001118">{{cite journal | vauthors = Mashaghi A, Kramer G, Lamb DC, Mayer MP, Tans SJ | title = Chaperone action at the single-molecule level | journal = Chemical Reviews | volume = 114 | issue = 1 | pages = 660–76 | date = January 2014 | pmid = 24001118 | doi = 10.1021/cr400326k }}</ref> [[Optical tweezers]] have been used to stretch single protein molecules from their C- and N-termini and unfold them to allow study of the subsequent refolding.<ref>{{cite journal | vauthors = Jagannathan B, Marqusee S | title = Protein folding and unfolding under force | journal = Biopolymers | volume = 99 | issue = 11 | pages = 860–9 | date = November 2013 | pmid = 23784721 | pmc = 4065244 | doi = 10.1002/bip.22321 }}</ref> The technique allows one to measure folding rates at single-molecule level; for example, optical tweezers have been recently applied to study folding and unfolding of proteins involved in blood coagulation. [[von Willebrand factor]] (vWF) is a protein with an essential role in blood clot formation process. It discovered – using single molecule optical tweezers measurement – that calcium-bound vWF acts as a shear force sensor in the blood. Shear force leads to unfolding of the A2 domain of vWF, whose refolding rate is dramatically enhanced in the presence of calcium.<ref>{{cite journal | vauthors = Jakobi AJ, Mashaghi A, Tans SJ, Huizinga EG | title = Calcium modulates force sensing by the von Willebrand factor A2 domain | journal = Nature Communications | volume = 2 | pages = 385 | date = July 2011 | pmid = 21750539 | pmc = 3144584 | doi = 10.1038/ncomms1385 | bibcode = 2011NatCo...2..385J }}</ref> Recently, it was also shown that the simple src [[SH3 domain]] accesses multiple unfolding pathways under force.<ref>{{cite journal | vauthors = Jagannathan B, Elms PJ, Bustamante C, Marqusee S | title = Direct observation of a force-induced switch in the anisotropic mechanical unfolding pathway of a protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 44 | pages = 17820–5 | date = October 2012 | pmid = 22949695 | pmc = 3497811 | doi = 10.1073/pnas.1201800109 | bibcode = 2012PNAS..10917820J | doi-access = free }}</ref>