3olm
From Proteopedia
Structure and Function of a Ubiquitin Binding Site within the Catalytic Domain of a HECT Ubiquitin Ligase
Structural highlights
Function[RSP5_YEAST] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Component of a RSP5 ubiquitin ligase complex which specifies polyubiquitination and intracellular trafficking of the general amino acid permease GAP1 as well as other cell surface proteins like GAP1, FUR4, MAL61, PMA1 and STE2. The RSP5-BUL1/2 complex is also necessary for the heat-shock element (HSE)-mediated gene expression, nitrogen starvation GLN3-dependent transcription, pressure-induced differential regulation of the two tryptophan permeases TAT1 and TAT2 and sorting efficiency into multivesicular bodies. Also acts on RBP1. Plays a role in tolerance to o-dinitrobenzene. Involved in actin cytoskeleton organization and dynamics. Ubiquitinates the LAS17-binding proteins LSB1 and PIN3/LSB2 without directing them for degradation and affects LAS17 levels in a SLA1-dependent and LSB1/2-independent manner.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [UBI4P_YEAST] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Publication Abstract from PubMedThe Rsp5 ubiquitin ligase contains a non-covalent binding site for ubiquitin within the amino-terminal lobe (N-lobe) of the HECT domain, and the X-ray crystal structure of the HECT-ubiquitin complex has been determined. Hydrophobic patch residues of ubiquitin (L8, I44, V70) were crucial for interaction with Rsp5, and amino-acid alterations at the Rsp5-binding interface resulted in defects in polyubiquitination. Our results support a model in which the N-lobe-binding site acts to localize and orient the distal end of the ubiquitin chain to promote conjugation of the next ubiquitin molecule. Structure and function of a HECT domain ubiquitin-binding site.,Kim HC, Steffen AM, Oldham ML, Chen J, Huibregtse JM EMBO Rep. 2011 Mar 11. PMID:21399621[13] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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