Crystal Structures of Lys-63-linked tri- and di-ubiquitin Reveal a Highly Extended Chain Architecture

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Proteins: Structure, Functions, and Bioinformatics

DOI:https://doi.org/10.1002/prot.22568· OSTI ID:1020111

Weeks, S; Grasty, K; Hernandez-Cuebas, L; Loll, P

The covalent attachment of different types of poly-ubiquitin chains signal different outcomes for the proteins so targeted. For example, a protein modified with Lys-48-linked poly-ubiquitin chains is targeted for proteasomal degradation, whereas Lys-63-linked chains encode nondegradative signals. The structural features that enable these different types of chains to encode different signals have not yet been fully elucidated. We report here the X-ray crystal structures of Lys-63-linked tri- and di-ubiquitin at resolutions of 2.3 and 1.9 {angstrom}, respectively. The tri- and di-ubiquitin species adopt essentially identical structures. In both instances, the ubiquitin chain assumes a highly extended conformation with a left-handed helical twist; the helical chain contains four ubiquitin monomers per turn and has a repeat length of {approx}110 {angstrom}. Interestingly, Lys-48 ubiquitin chains also adopt a left-handed helical structure with a similar repeat length. However, the Lys-63 architecture is much more open than that of Lys-48 chains and exposes much more of the ubiquitin surface for potential recognition events. These new crystal structures are consistent with the results of solution studies of Lys-63 chain conformation, and reveal the structural basis for differential recognition of Lys-63 versus Lys-48 chains.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1020111
• Report Number(s): BNL--95960-2011-JA
• Journal Information: Proteins: Structure, Functions, and Bioinformatics, Journal Name: Proteins: Structure, Functions, and Bioinformatics Journal Issue: 4 Vol. 77; ISSN 0887-3585
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
ARCHITECTURE
CHAINS
CRYSTAL STRUCTURE
CRYSTALLOGRAPHY
MONOMERS
PROTEINS
national synchrotron light source