Editing Microfilament (section)

==A proposed model – ''actoclampins'' track filament ends==
One proposed model suggests the existence of actin filament barbed-end-tracking molecular motors termed "actoclampin".<ref name="DCP2004">{{Cite journal |vauthors=Dickinson RB, Caro L, Purich DL |date=October 2004 |title=Force generation by cytoskeletal filament end-tracking proteins |journal=Biophysical Journal |volume=87 |issue=4 |pages=2838–54 |bibcode=2004BpJ....87.2838D |doi=10.1529/biophysj.104.045211 |pmc=1304702 |pmid=15454475}}</ref> The proposed actoclampins generate the propulsive forces needed for actin-based motility of [[lamellipodia]], [[filopodia]], invadipodia, [[dendritic spine]]s, [[intracellular]] [[vesicle (biology)|vesicle]]s, and [[Motility|motile]] processes in [[endocytosis]], [[exocytosis]], podosome formation, and [[phagocytosis]]. Actoclampin motors also propel such intracellular [[pathogen]]s as ''[[Listeria monocytogenes]]'', ''[[Shigella flexneri]]'', ''[[Vaccinia]]'' and ''[[Rickettsia]]''. When assembled under suitable conditions, these end-tracking molecular motors can also propel [[biomimetic]] particles.{{cn|date=December 2024}}

The term [[actoclampin]] is derived from ''acto''- to indicate the involvement of an actin filament, as in actomyosin, and ''clamp'' to indicate a clasping device used for strengthening flexible/moving objects and for securely fastening two or more components, followed by the suffix -''in'' to indicate its protein origin. An actin filament end-tracking protein may thus be termed a clampin.{{cn|date=December 2024}}

Dickinson and Purich recognized that prompt [[ATP hydrolysis]] could explain the forces achieved during actin-based motility.<ref name=D&P2002/>  They proposed a simple [[mechanoenzymatic]] sequence known as the Lock, Load & Fire Model, in which an end-tracking protein remains tightly bound ("locked" or clamped) onto the end of one sub-filament of the double-stranded actin filament. After binding to Glycyl-Prolyl-Prolyl-Prolyl-Prolyl-Prolyl-registers on tracker proteins, Profilin-ATP-actin is delivered ("loaded") to the unclamped end of the other sub-filament, whereupon [[Adenosine triphosphate|ATP]] within the already clamped terminal subunit of the other subfragment is hydrolyzed ("fired"), providing the energy needed to release that arm of the end-tracker, which then can bind another Profilin-ATP-actin to begin a new monomer-addition round.{{cn|date=January 2023}}

===Steps involved===
The following steps describe one force-generating cycle of an actoclampin molecular motor:
# The polymerization cofactor profilin and the ATP·actin combine to form a profilin-ATP-actin complex that then binds to the end-tracking unit
# The cofactor and monomer are transferred to the barbed-end of an actin already clamped filament
# The tracking unit and cofactor dissociate from the adjacent protofilament, in a step that can be facilitated by ATP hydrolysis energy to modulate the affinity of the cofactor and/or the tracking unit for the filament; and this mechanoenzymatic cycle is then repeated, starting this time on the other sub-filament growth site.{{cn|date=January 2023}}

When operating with the benefit of ATP hydrolysis, AC motors generate per-filament forces of 8–9 pN, which is far greater than the per-filament limit of 1–2 pN for motors operating without ATP hydrolysis.<ref name=D&P2002/><ref name=DCP2004/><ref>{{Cite journal |vauthors=Dickinson RB, Purich DL |date=August 2006 |title=Diffusion rate limitations in actin-based propulsion of hard and deformable particles |journal=Biophysical Journal |volume=91 |issue=4 |pages=1548–63 |bibcode=2006BpJ....91.1548D |doi=10.1529/biophysj.106.082362 |pmc=1518650 |pmid=16731556}}</ref>  The term actoclampin is generic and applies to all actin filament end-tracking molecular motors, irrespective of whether they are driven actively by an ATP-activated mechanism or passively.{{cn|date=December 2024}}

Some actoclampins (e.g., those involving Ena/VASP proteins, WASP, and N-WASP) apparently require Arp2/3-mediated filament initiation to form the [[actin polymerization]] nucleus that is then "loaded" onto the end-tracker before processive motility can commence. To generate a new filament, Arp2/3 requires a "mother" filament, monomeric ATP-actin, and an activating domain from Listeria ActA or the VCA region of N-WASP. The Arp2/3 complex binds to the side of the mother filament, forming a Y-shaped branch having a 70-degree angle with respect to the [[Anatomical terms of location|longitudinal]] axis of the mother filament. Then upon activation by ActA or VCA, the Arp complex is believed to undergo a major conformational change, bringing its two actin-related protein subunits near enough to each other to generate a new filament gate. Whether ATP hydrolysis may be required for nucleation and/or Y-branch release is a matter under active investigation.{{cn|date=December 2024}}