Structural and mechanistic insights into the arginine/lysine-rich peptide motifs that interact with P97/VCP.
Biochim Biophys Acta
; 1834(12): 2672-8, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24100225
ABSTRACT
P97 protein, also referred to as valosin-containing protein (VCP), is an AAA-ATPase (ATPase associated with a variety of cellular activities) that mediates vital cellular activities with the cooperation of many cofactors. A group of cofactors interact with the N-terminal domain of P97 (P97N) through their Arg/Lys-rich peptide motifs. We investigated the interactions between P97 and these motifs, including VCP-binding motif (VBM) and VCP-interacting motif (VIM). The solution structures of the VBM motif from HRD1 and the VIM motif from SVIP are both comprised mainly of a single α-helix. The VIM motifs generally have stronger P97N-binding affinities than the VBMs, and SVIP (VIM) can compete with HRD1-VBM for the interaction, providing a possibility that VIM-containing proteins (such as SVIP) act as competitors against VBM-containing proteins (such as HRD1) for interacting with P97. Based on biochemical features of the VBM motifs, we also identified NUB1L (NEDD8 ultimate buster-1 long) as a novel VBM-containing protein, which is involved in proteasomal degradation of NEDD8 through the P97 pathway.
Palavras-chave
AAA; ATPase associated with a variety of cellular activities; Arginine/lysine-rich; BS1; ERAD; ITC; Interaction; NMR; P97-ND1; P97/VCP; P97N; Structure; VBM; VCP; VCP-binding motif; VCP-interacting motif; VIM; binding site 1; endoplasmic reticulum-associated degradation; isothermal titration calorimetry; nuclear magnetic resonance; the N and D1 domains of P97 (residues 1458); the N-terminal domain of P97 (residues 1213); valosin-containing protein
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peptídeos
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Fatores de Transcrição
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Proteínas de Transporte
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Adenosina Trifosfatases
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Proteínas de Ciclo Celular
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Ubiquitina-Proteína Ligases
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China