| Accession: | |
|---|---|
| Functional site class: | PAM2 motif |
| Functional site description: | The PABP-interacting motif 2 (PAM2) mediates binding of proteins to the MLLE/PABC peptide-binding domain found in poly(A)-binding proteins and HYD E3 ubiquitin ligases. There are two variants of the PAM2 motif that bind to overlapping but distinct sites on the MLLE domain, adopt a different orientation at their termini and consequently have different recognition elements in these regions. While the core region around a critical phenylalanine is similar in the LIG_PAM2_1 and LIG_PAM2_2 variants and makes identical contacts with the MLLE domain, the N-terminal sequence in the LIG_PAM2_1 provides a hydrophobic residue that is essential for efficient binding and is lacking in LIG_PAM2_2 motifs, while the C-terminal part of the LIG_PAM2_2 variant makes a turn and follows an alternative path on the MLLE surface that depends on an aromatic residue that is absent from LIG_PAM2_1 motifs. |
| ELMs with same func. site: | LIG_PAM2_1 LIG_PAM2_2 |
| ELM Description: | Binding of the LIG_PAM2_1 mainly involves hydrophobic interactions, the most important of which are mediated by the residues in position 3 (lacking in LIG_PAM2_2) and 10 (corresponds to position 5 in LIG_PAM2_2). The residues in positions 1 and 2 of the motif, most often polar or charged residues, do not participate in binding, except for eRF3, which contains two overlapping motifs, where phenylalanine in position 1 of the C-terminal motif bends back to bind in the hydrophobic pocket that is normally occupied by the hydrophobic residue at position 3, which is most frequently leucine, but in some cases phenylalanine or proline. The side chain of the asparagine or serine residue in position 4 is involved in an intermolecular salt bridge and forms an intramolecular hydrogen bond with the amide of the residue in position 6. The latter interaction stabilizes the beta-turn conformation of the peptide. The regular occurrence of proline in position 5 might be due to its propensity to form such a beta-turn. Position 7 is invariantly alanine, which is involved in different hydrophobic interactions with multiple MLLE residues. Introduction of a bulky residue at this position was found to decrease the affinity for the peptide. Position 10 is the single most important residue for binding and in most cases it is occupied by phenylalanine, but exceptionally by tryptophan in LARP4 and LARP4B, or possibly also by tyrosine in the Arabidopsis thaliana proteins CID5 and CID6. Since CID5 is the only example of an experimentally validated motif with a tyrosine in position 10, this feature might be specific for plants. The residue in position 10 occupies a hydrophobic pocket between helices 2 and 3 and is the major binding determinant. In case of a phenylalanine in this position, a hydrophobic residue is found in position 12, with a clear preference for proline. AtCID5 and AtCID6 also contain a proline at position 12. For Fungi and some TAXON:7215 sequences, the regular expression is less strict. |
| Pattern: | ..[LFP][NS][PIVTAFL].A..(([FY].[PYLF])|(W..)). |
| Pattern Probability: | 0.0000100 |
| Present in taxon: | Eukaryota |
| Interaction Domain: |
PABP (PF00658)
Poly-adenylate binding protein, unique domain
(Stochiometry: 1 : 1)
PDB Structure: 3KUS
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