Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a.

Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a. Abstract Text:

Aydin Haririnia,Mariapina D'Onofrio,David Fushman,

Numerous cellular processes are regulated by (poly)ubiquitin-mediated signaling events, which involve a covalent modification of the substrate protein by a single ubiquitin or a chain of ubiquitin molecules linked via a specific lysine. Remarkably, the outcome of polyubiquitination is linkage-dependent. For example, Lys48-linked chains are the principal signal for proteasomal degradation, while Lys63-linked chains act as nonproteolytic signals. Despite significant progress in characterization of various cellular pathways involving ubiquitin, understanding of the structural details of polyubiquitin chain recognition by downstream cellular effectors is missing. Here we use NMR to study the interaction of a ubiquitin-interacting motif (UIM) of the proteasomal subunit S5a with di-ubiquitin, the simplest model for polyubiquitin chain, to gain insights into the mechanism of polyubiquitin recognition by the proteasome. We have mapped the binding interface and characterized the stoichiometry and the process of UIM binding to Lys48- and Lys63-linked di-ubiquitin chains. Our data provide the first direct evidence that UIM binding involves a conformational transition in Lys48-linked di-ubiquitin, which opens the hydrophobic interdomain interface. This allows UIM to enter the interface and bind directly to the same ubiquitin hydrophobic-patch surface as utilized in UIM:monoubiquitin complexes. The results indicate that up to two UIM molecules can bind di-ubiquitin, and the binding interface between UIM and ubiquitin units in di-ubiquitin is essentially the same for both Lys48- and Lys63-linked chains. Our data suggest possible structural models for the binding of UIM and of full-length S5a to di-ubiquitin.

Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a. Publishing Authors By Initials

A Haririnia,M D'Onofrio,D Fushman,

For similar proteins: ubiquitins: ubiquitin research abstracts see: proteins: ubiquitins: ubiquitin research

PUBMED ID PMID:

MEDLINE DATE:

Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of molecular biology

VOLUME: 368

Page Numbers: 753-66

Journal Abbreviation:

ISSN: 0022-2836

DAY: 22

MONTH: 02

YEAR: 2007

Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985088

Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a. Keywords Mesh Terms:

KEYWORDS: Ubiquitin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a. Information

Substance Name: Proteasome Endopeptidase Complex

Registry Number: EC 3.4.25.1

Grant and Affiliation Information for Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a.

AFFILIATION: Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD 20742, USA.

Country: England

AGENCY: United States NIGMS

GRANT: R01 GM065334-05

ACRONYM: GM

MEDLINETA: J Mol Biol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a Related Publications

• A model of interdomain mobility in a multidomain protein.
• Affinity Makes the Difference: Nonselective Interaction of the UBA Domain of Ubiquilin-1 with Monomeric Ubiquitin and Polyubiquitin Chains.
• An efficient computational method for predicting rotational diffusion tensors of globular proteins using an ellipsoid representation.
• Analysis of interdomain dynamics in a two-domain protein using residual dipolar couplings together with 15N relaxation data.
• Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin.
• Mapping the interactions between Lys48 and Lys63-linked di-ubiquitins and a ubiquitin-interacting motif of S5a.
• Measurement of 15N relaxation in deuterated amide groups in proteins using direct nitrogen detection.
• Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins.
• Structural assembly of multidomain proteins and protein complexes guided by the overall rotational diffusion tensor.