ESCRT complexes and accessory proteins ESCRT

1 escrt complexes , accessory proteins

1.1 escrt-0
1.2 escrt-i
1.3 escrt-ii
1.4 escrt-iii
1.5 vps4-vta1
1.6 bro1

escrt complexes , accessory proteins

summary of escrt machinery , accessory proteins.

each of escrt complexes , accessory proteins have unique structures enable distinct biochemical functions. number of synonyms exist each protein component of escrt machinery, both yeast , metazoans. summary table of of these proteins provided below.

in yeast, following complexes/accessory proteins exist follows:

escrt-0

the escrt-0 complex plays vital role in generation of multivesicular bodies binding , clustering ubiquitinated proteins and/or receptors on surface of cell. complex responsible binding lipid on endosomal membrane, recruits these tagged proteins endosome. once localized, these proteins taken endosome via vesicles, forming multivesicular bodies, , delivered lysosome degraded. process essential major pathway degradation of damaged proteins have passed through golgi. components of escrt-0 complex exist follows:

the complex 1:1 heterodimer of vps27 (vacuolar protein sorting protein 27) , hse1. vps27 , hse1 dimerize through antiparallel coiled-coil gat (so named after proteins gga , tom1) domains. both vps27 , hse1 contain amino-terminal vhs domain (so named because contained in vps27, hrs, , stam proteins). these vhs domains bind ubiquitin on proteins cell aims degrade. ubiquitin can associate ubiquitin interacting motifs such 1 on hse1 or double sided domain found on vps27. fyve domain (named after 4 proteins in identified: fab1p, yotb, vac1, , eea1) found sandwiched between vhs , ubiquitin interacting motif domains of vps27. phosphatidylinositol 3-phosphate, common endosomal lipid, binds fyve domain resulting in recruitment of escrt-0 endosome.

escrt-i

the role of escrt-i complex assist in generation of multivesicular bodies clustering ubiquitinated proteins , acting bridge between escrt-0 , escrt-ii complexes. plays role in membrane recognition , remodeling during membrane abscission forming rings on either side of midbody of dividing cells. escrt-i responsible recruiting escrt-iii, forms constriction zone before cells separate. furthermore, escrt-i plays role in viral budding interacting specific viral proteins, leading recruitment of additional escrt machinery potential site of viral release. details of escrt-i machinery described below.

the escrt-i complex heterotetramer (1:1:1:1) of vps23, vps28, vps37, , mvb12. assembled heterotetramer appears rod-shaped stalk composed of vps23, vps37, , mvb12 fanned cap composed of single helices of vps23, vps28, , vps37. vps23 contains 1 ubiquitin e2 variant domain, responsible binding of ubiquitin, escrt-0 complex, , ptap (proline, threonine, alanine, proline) motif of viral gag proteins. after ubiquitin e2 variant domain, proline rich motif (gppx3y) present directs escrt-i midbody during membrane abscission. mvb12 can bind ubiquitin via carboxy-terminus. vps28 responsible interaction of escrt-i , escrt-ii associating glue domain (gram-like ubiquitin-binding in eap45) of vps36 through carboxy-terminal four-helix bundle domain.

escrt-ii

the escrt-ii complex functions during biogenesis of multivesicular bodies , delivery of ubiquitin tagged proteins endosome. ubiquitin tagged proteins passed escrt-0 escrt-i , escrt-ii. escrt-ii associates escrt-iii, pinches cargo containing vesicle closed. specific aspects of escrt-ii follows:

escrt-ii heterotetramer (2:1:1) composed of 2 vps25 subunits, 1 vps22, , 1 vps36 subunit. vps25 molecules contain ppxy motifs, bind winged-helix (wh) motifs of vps22 , vps36 creating y-shaped complex vps22 , vps36 base , vps25 molecules arms. vps25 molecules contain wh motifs responsible interaction of escrt-ii escrt-iii. vps36 contains glue domain binds phosphatidylinositol 3-phosphate , vps28 of escrt-i. 2 zinc finger domains looped glue domain of yeast vps36. 1 of these zinc finger domains binds carboxy-terminal domain of vps28 , other associates ubiquitin.

escrt-iii

the escrt-iii complex important of escrt machinery because plays role in escrt mediated processes. during membrane abscission , viral budding, escrt-iii forms long filaments coil around site of membrane constriction prior membrane cleavage. mediation of abscission occurs through interactions centralspindlin complex. these filamentous structures present during multivesicular body formation , function ring-like fence plugs budding vesicle prevent cargo proteins escaping cell s cytosol. escrt-iii exists , functions follows:

the escrt-iii complex differs other escrt machinery in exists transiently , contains both essential , nonessential components. essential subunits must assemble in proper order (vps20, snf7, vps24, vps2) machinery function. nonessential subunits include vps60, did2, , ist1. vps20 initiates assembly of escrt-iii acting nucleator of snf7 polymer assembly. vps24 associates snf7 cap complex , recruit vps2. vps2 brings vps4 complex. “free” cytosolic forms of each subunit considered closed. is, carboxy-terminal portion of each subunit folds onto in autoinhibitory manner stabilizing monomeric subunits. carboxy-terminus of escrt-iii subunits, both essential , nonessential, contain mims (mit (microtubule interacting , transport domain) interacting motif) motifs. these motifs responsible binding vps4 , aaa-atpase spastin.

vps4-vta1

the vps4-vta1 proteins required stripping of other escrt components (usually escrt-iii) membranes once particular process has been completed. there debate whether vps4 cleaves escrt-iii complex away or remodels complex 1 component shed @ particular time. vta1 thought act activator of vps4, aiding assembly , enhancing aaa-atpase activity. manner in these proteins function follows:

vps4 subunits have 2 functional domains, amino-terminal mit domain , central aaa-atpase domain. mit domain responsible interaction of vps4 mim domain of vps2. aaa-atpase domain hydrolyzes atp power disassembly of escrt-iii complex. “stripping” of escrt-iii allows associated subunits recycled further use. vta1 dimeric protein containing 1 vsl domain (so named because found in proteins vps4, sbp1, , lip5), enables binding vps4, , mit domain associating escrt-iii subunit vps60. though not essential, vta1 has been shown aid in vps4 ring assembly, accelerate atpase activity of vsp4, , encourage escrt-iii disassembly.

bro1

the main function of bro1 recruit deubiquitinases escrt-iii complex. results in removal of ubiquitin tags proteins targeted degradation in lysosome prior generation of multivesicular bodies. has been speculated bro1 helps stabilize escrt-iii while ubiquitin tags cleaved cargo proteins.

bro1 contains bro1 amino-terminal domain binds snf7 of escrt-iii. binding brings bro1 site of membrane abscission. bro1 binds catalytic domain of doa4, ubiquitin hydrolase (deubiquitinase), bringing site of abscission. doa4 removes ubiquitin cargo proteins being targeted lysosome.