This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5o44

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 13:16, 10 May 2019

Crystal structure of unbranched mixed tri-Ubiquitin chain containing K48 and K63 linkages.

Structural highlights

5o44 is a 6 chain structure with sequence from Human and House fly. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	UBB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBB_HUMAN] 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, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. 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.^[1] ^[2]

Publication Abstract from PubMed

The ability of ubiquitin to function in a wide range of cellular processes is ascribed to its capacity to cause a diverse spectrum of modifications. While a target protein can be modified with monoubiquitin, it can also be modified with ubiquitin chains. The latter include seven types of homotypic chains as well as mixed ubiquitin chains. In a mixed chain, not all the isopeptide bonds are restricted to a specific lysine of ubiquitin, resulting in a chain possessing more than one type of linkage. While structural characterization of homotypic chains has been well elucidated, less is known about mixed chains. Here we present the crystal structure of a mixed tri-ubiquitin chain at 3.1-A resolution. In the structure, the proximal ubiquitin is connected to the middle ubiquitin via K48 and these two ubiquitins adopt a compact structure as observed in K48 di-ubiquitin. The middle ubiquitin links to the distal ubiquitin via its K63 and these ubiquitins adopt two conformations, suggesting a flexible structure. Using small-angle X-ray scattering, we unexpectedly found differences between the conformational ensembles of the above tri-ubiquitin chains and chains possessing the same linkages but in the reverse order. In addition, cleavage of the K48 linkage by DUB is faster if this linkage is at the distal end. Taken together, our results suggest that in mixed chains, not only the type of the linkages but also their sequence determine the structural and functional properties of the chain.

The Crystal Structure and Conformations of an Unbranched Mixed Tri-Ubiquitin Chain Containing K48 and K63 Linkages.,Padala P, Soudah N, Giladi M, Haitin Y, Isupov MN, Wiener R J Mol Biol. 2017 Oct 27. pii: S0022-2836(17)30520-X. doi:, 10.1016/j.jmb.2017.10.027. PMID:29111344^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
↑ Padala P, Soudah N, Giladi M, Haitin Y, Isupov MN, Wiener R. The Crystal Structure and Conformations of an Unbranched Mixed Tri-Ubiquitin Chain Containing K48 and K63 Linkages. J Mol Biol. 2017 Oct 27. pii: S0022-2836(17)30520-X. doi:, 10.1016/j.jmb.2017.10.027. PMID:29111344 doi:http://dx.doi.org/10.1016/j.jmb.2017.10.027

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5o44"

@@ Line 1: / Line 1: @@
 ==Crystal structure of unbranched mixed tri-Ubiquitin chain containing K48 and K63 linkages.==
-<StructureSection load='5o44' size='340' side='right' caption='[[5o44]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
+<StructureSection load='5o44' size='340' side='right'caption='[[5o44]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5o44]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/House_fly House fly]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O44 FirstGlance]. <br>
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5o44" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ubiquitin|Ubiquitin]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 [[Category: House fly]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Isupov, M N]]
 [[Category: Padala, P]]

5o44

From Proteopedia

Revision as of 13:16, 10 May 2019

Crystal structure of unbranched mixed tri-Ubiquitin chain containing K48 and K63 linkages.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox