Table 1: Clathrin and COP coats: subunit functions and domains

 

AP1/GGA-associated proteins

AP2-associated proteins

COPI-associated proteins

COPII-associated proteins

Adaptor/coat

Salient features

Peptide motifs

Functions

Clathrin

 

 

Endocytosis, sorting from TGN to endosomes, sorting from early to late endosomes

Heavy chain

Subunits polymerise into a triskelion; Atomic structures of several fragments reveal alpha-zigzag repeats and a beta-propeller terminal domain. [1, 2]

Binds LLDLD type 1 clathrin motif and PWxxW type 2 clathrin motif [3, 4].

Recognition of peptide motifs through the beta-propeller formed by WD40 repeats (terminal domain). Binding partners include auxilin, amphiphysin, epsin and AP180 [5-7]. The triskelial arms define skeleton of the clathrin coat.

Light chain: LCa/b

Interacts with Hsc70, calmodulin and the central helical/coiled coil domain of HIP1/HIP12 [8-11]

 

Regulates clathrin self-assembly into polyhedral lattices [12].

AP1 Adaptors

 

 

TGN-endosome sorting

gamma

Large AP complex subunit with truncated appendage domain [13]

Binds DFGx(bulky hydrophobic) and DFxDF motifs [14] [15].

Membrane binding via Arf1 [16].

Recruitment of accessory factors to AP1 complexes eg. EpsinR.

beta1

 

Clathrin box motif in hinge: LLNLD [17].

Binds dileucine cargo motifs:

[DE]xxxL[LI] [18].

Membrane binding via Arf1[19].

Binds to clathrin via hinge domain.

Binds accessory proteins via appendage domain.

Cargo recognition.

mu1 (A/B)

 

Binds Yxx(bulky hydrophobic) cargo motifs [20].

Cargo recognition.

Membrane interaction.

sigma1

sigma1 sequence is weakly related to the N-terminal portion of mu.

 

Stabilises the AP core complex by mediating interactions between subunits [21].

AP2 adaptors

 

 

Plasma membrane endocytosis

alphaA/C

Atomic structure of the appendage and trunk domain are known [22, 23].

Binds DxF,

FxDxF and

WVxF motifs [24-27]

Membrane binding.

Recruitment of accessory proteins eg. Epsin1 [28]

beta2

Atomic structure of the appendage and trunk domain are known [23, 29].

Clathrin box motif in hinge: LLNLD [30]. Binds cargo motif:

[DE]xxxL[LI] [31].

Binds to cargo dileucine motifs.

Binds clathrin via hinge domain.

Binds accessory proteins via appendage domain [32].

mu2

Atomic structure of m2 and of interactions with Yxx(bulky hydrophobic)

sorting motifs is known [33].

Binds Yxx(bulky hydrophobic) in cargo [20]

and WVxF in stonin 2 [34].

Membrane interaction.

Cargo recognition.

Also interacts with accessory proteins such as stonin 2.

sigma2

sigma2 sequence is weakly related to N-terminal portion of mu.

 

Stabilises the AP core complex by mediating interactions between subunits.

AP3 adaptors[35, 36]

 

 

Melanosome biogenesis

delta

Appendage domain and trunk domains conserved [36].

 

Like binds to accessory proteins via the appendage domain, but these have not been identified as yet [37].

beta3 (A/B)

Appendage domain and trunk domains conserved [38].

Clathrin box motif in hinge: LLDLD.

Binds cargo motif:

[DE]xxxL[LI] [39].

Binds clathrin.

Appendage domain with conserved ligand binding pocket likely binds to accessory proteins.

Cargo recognition

mu3 (A/B)

 

Binds cargo motif Yxx(bulky hydrophobic) [40].

Cargo recognition.

sigma3 (A/B)

 

 

Stabilises the AP3 complex.

AP4 adaptors [41-43]

 

 

Basolateral sorting/ TGN-endosome sorting

epsilon

 

 

Membrane binding via Arf1.

Conserved appendage domain so likely recruits accessory proteins.

beta4

 

No obvious clathrin box

Binds the neuronal protein tyrosine phosphatases PTP-SL and PTPBR7 [44].

Has conserved appendage domain.

mu4

 

Binds Yxx(bulky hydrophobic) weakly and also interacts with other non-classical cargo motifs like DLYYDPM [45]

Cargo recognition.

sigma4

 

 

Stabilises the AP4 complex.

GGAs

 

 

TGN-endosome/lysosome sorting

GGA-1

 

Multidomain alternative adaptors with VHS, GAT, hinge and appendage domains.

Clathrin box motif in hinge: LLDDE.

 

Appendage domain binds DFGx(bulky hydrophobic) motifs[46, 47].

 

VHS domain binds

DxxLL motifs [48].

 

WNSF sequence in the hinge is bound by the AP1 gamma appendage [49].

 

Clathrin binding. Recruitment of accessory factors such as rabaptin-5 and p56 by appendage domain.

Cargo recognition (eg. Ci-M6PR) via VHS domain. Membrane recruitment via Arf binding to GAT domain[50].

Ubiquitin binding via GAT domain and thus potentially binds ubiquitinated cargo[51].

GGA-2

 

Clathrin box motifs in hinge: LIDLE and LLDLL. Other interactions are same as for GGA-1 [52].

Same as for GGA-1

GGA-3

 

Unidentified clathrin-binding motif and other interactions are same as for GGA-1 [53].

Same as for GGA-1

Hrs

VHS, FYVE, Ubiquitin binding and clathrin binding.

FYVE domain binds to PtdIns(3)P.

Involved in flat clathrin lattice formation on early endosomes.

COPI

F-subcomplex: beta,delta,gamma,zeta[54]

B-subcomplex:alpha,beta-prime,epsilon[55]

 

 

Retrograde transport from the Golgi to the ER, maintenance of Golgi integrity

Arf1

Small GTPase; Ras family

 

Recruitment of COPI coatomer to membranes in a GTP dependent manner [56].

alphaCOP / Ret1p

WD40 repeats (b-propeller domain) [57].

Binds KKxx, KxKxx motifs [58, 59].

Recruitment of cargo and accessory factors (eg Dsl1p).

betaCOP

Binds Arf1, and has weak sequence identity to b-adaptin.

Has appendage domain like large AP subunits.

 

Binds to diacidic cargo motifs [60].

Recruitment of cargo and accessory factors via appendage domain but these have not been identified.

Binds to KDEL receptor [61]

Beta-primeCOP / Sec26p

WD40 repeats (beta-propeller) [57]

Binds KxKxx motif.

Recruitment of cargo.

gammaCOP / Sec21p

Binds members of the p24 family [62].

Has appendage domain like large AP subunits [63, 64].

 

Recruitment of cargo.

Recruitment of cargo and accessory factors (ArfGAP) via appendage domain.

deltaCOP / Ret2p

Weak sequence identity to mu-adaptin.

Binds WxxxW motif in the acidic domain of Dsl1p [65, 66].

Binds accessory protein via acidic tryptophan motif.

epsilonCOP / Sec28p

 

 

May stabilise the complex in that point mutations are often lethal in yeast [67].

zetaCOP / Ret3p

Weak sequence identity to sigma-adaptin [68].

 

Stabilises the interaction between beta-COP and gamma-COP.

ARFGAPs Glo3p

GTPase activating protein for ARF[69].

Binds beta-prime WD40 domain and gamma-COP appendage domain.

 

Activates Arf GTP hydrolysis to promote coat disassembly.

Complexes with the KDEL receptor [61]

ARFGEFs Gea1p/Gea2p

GEF for ARF [70, 71]

 

 

COPII

 

 

Protein export from the ER

hSar1p

Small GTPase of the Ras family [72].

 

Recruits coat components to membranes in a GTP dependent manner[73].

hSec13p/

hSec31p

Both subunits have WD40 repeats (beta-propeller domains)[72, 74].

Not identified as yet

Induces coat polymerisation.

hSec23p/hSec24p

Sec23 is a Sar1p GTPase activating protein and Sec24 binds cargo [75]

Sec24 binds DxE,

YNNSNPF and

Lxx[L/M]E motifs [75-77].

Has GAP activity for Sar1p,

Cargo recognition

and membrane curvature selection.

hSec12p

Has a GEF domain.

 

ER localised GEF and thus leads to the recruitment of Sar1p and COPII coat components to the ER [78].

hSec16p

Forms a ternary complex with Sec23/24p in vitro [79]

 

Stabilizes Sec23/24 complex and stimulates vesicle budding [80]

 

 

 

 

 

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