Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin.

Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin. Abstract Text:

Bryan C Dickinson,Ranjani Varadan,David Fushman,

In solution, Lys48-linked di-ubiquitin exists in dynamic equilibrium between closed and open conformations. To understand the effect of interdomain motion in polyubiquitin chains on their ability to bind ligands, we cyclized di-ubiquitin by cross-linking the free C terminus of the proximal ubiquitin with the side chain of residue 48 in the distal ubiquitin, using a chemical cross-linker, 1,6-Hexane-bis-vinylsulfone. Our NMR studies confirm that the cyclization affects conformational dynamics in di-ubiquitin by restricting opening of the interface and shifting the conformational equilibrium toward closed conformations. The cyclization, however, did not rigidly lock di-ubiquitin in a single closed conformation: The chain undergoes slow exchange between at least two closed conformations, characterized by interdomain contacts involving the same hydrophobic patch residues (Leu8-Ile44-Val70) as in the uncyclized di-ubiquitin. Lowering the pH changes the relative populations of these conformations, but in contrast with the uncyclized di-ubiquitin, does not lead to opening of the interface. This restriction of domain motions inhibits direct access of protein molecules to the hydrophobic patch residues located at the very center of the interdomain interface in di-ubiquitin, although the residual motions are sufficient to allow access of small molecules to the interface. This renders di-ubiquitin unable to bind protein molecules (e.g., UBA2 domain) in the normal manner, and thus could interfere with Ub(2) recognition by various downstream effectors. These results emphasize the importance of the opening/closing domain motions for the recognition and function of di-ubiquitin and possibly longer polyubiquitin chains.

Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin. Publishing Authors By Initials

BC Dickinson,R Varadan,D Fushman,

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

PUBMED ID PMID:

MEDLINE DATE:

Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Protein science : a publication of the Protein Soc

VOLUME: 16

Page Numbers: 369-78

Journal Abbreviation: Protein Sci.

ISSN: 0961-8368

DAY: 22

MONTH: 01

YEAR: 2007

Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9211750

Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin. Keywords Mesh Terms:

KEYWORDS: Ubiquitins

MESH TERMS: chemistry

Chemical & Substance for Abstract: Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin. Information

Substance Name: Ubiquitin-Activating Enzymes

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin.

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

Country: United States

AGENCY: United States NIGMS

GRANT: GM065334

ACRONYM: GM

MEDLINETA: Protein Sci

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin 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.