The diversity of ubiquitin recognition: hot spots and varied specificity.

Ubiquitin is attached to a large number of proteins and gives rise to signaling events that modulate many cellular functions. These signals are often based on the recognition of polyubiquitin chains, which are produced in a variety of lengths and linkage patterns. In addition, proteins that are similar to ubiquitin in structure and function are often recognized by an overlapping set of partners. Research over the past several years has expanded our understanding of how ubiquitin and ubiquitin-like proteins are recognized. Most interactions occur at a few distinct surface areas; however, individual binding partners have specific, unique contacts that impart specificity. In this review, we summarize available information to facilitate comparisons across the ubiquitin-like family.

[1]  Nathan A. Baker,et al.  Electrostatics of nanosystems: Application to microtubules and the ribosome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A. Ciechanover,et al.  Mechanisms of intracellular protein breakdown. , 1982, Annual review of biochemistry.

[3]  Franca Fraternali,et al.  Josephin domain of ataxin‐3 contains two distinct ubiquitin‐binding sites , 2009, Biopolymers.

[4]  Aydin Haririnia,et al.  Structure of the s5a:k48-linked diubiquitin complex and its interactions with rpn13. , 2009, Molecular cell.

[5]  Soichi Wakatsuki,et al.  Ubiquitin-binding domains — from structures to functions , 2009, Nature Reviews Molecular Cell Biology.

[6]  S. Akira,et al.  Involvement of linear polyubiquitylation of NEMO in NF-κB activation , 2009, Nature Cell Biology.

[7]  L. Sánchez-Pulido,et al.  RAWUL: A new ubiquitin-like domain in PRC1 Ring finger proteins that unveils putative plant and worm PRC1 orthologs , 2008, BMC Genomics.

[8]  Cynthia Wolberger,et al.  Crystal structure and solution NMR studies of Lys48-linked tetraubiquitin at neutral pH. , 2007, Journal of molecular biology.

[9]  J. Forman-Kay,et al.  Interactions between the three CIN85 SH3 domains and ubiquitin: implications for CIN85 ubiquitination. , 2008, Biochemistry.

[10]  Linda Hicke,et al.  Ubiquitin-binding domains , 2005, Nature Reviews Molecular Cell Biology.

[11]  H. Paulson,et al.  The Deubiquitinating Enzyme Ataxin-3, a Polyglutamine Disease Protein, Edits Lys63 Linkages in Mixed Linkage Ubiquitin Chains* , 2008, Journal of Biological Chemistry.

[12]  Z. Elazar,et al.  The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes , 2008, Journal of Cell Science.

[13]  D. Fushman,et al.  Polyubiquitin chains: polymeric protein signals. , 2004, Current opinion in chemical biology.

[14]  Muyang Li,et al.  Crystal Structure of a UBP-Family Deubiquitinating Enzyme in Isolation and in Complex with Ubiquitin Aldehyde , 2002, Cell.

[15]  D. Fushman,et al.  Avid interactions underlie the K63-linked polyubiquitin binding specificities observed for UBA domains , 2009, Nature Structural &Molecular Biology.

[16]  P. Howley,et al.  DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Linda Hicke,et al.  Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. , 2003, Annual review of cell and developmental biology.

[18]  Michael Assfalg,et al.  Structural determinants for selective recognition of a Lys48-linked polyubiquitin chain by a UBA domain. , 2005, Molecular cell.

[19]  Kay Hofmann,et al.  Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain , 2009, Nature Structural &Molecular Biology.

[20]  C. Arrowsmith,et al.  Ring1B contains a ubiquitin-like docking module for interaction with Cbx proteins. , 2009, Biochemistry.

[21]  S. D’Souza,et al.  Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1. , 2010, Molecular cell.

[22]  Christina Kiel,et al.  The ubiquitin domain superfold: structure-based sequence alignments and characterization of binding epitopes. , 2006, Journal of molecular biology.

[23]  Oliver F. Lange,et al.  Recognition Dynamics Up to Microseconds Revealed from an RDC-Derived Ubiquitin Ensemble in Solution , 2008, Science.

[24]  Colin Gordon,et al.  Mechanism of Lys48‐linked polyubiquitin chain recognition by the Mud1 UBA domain , 2005, The EMBO journal.

[25]  Christina Kiel,et al.  Recognizing and defining true Ras binding domains I: biochemical analysis. , 2005, Journal of molecular biology.

[26]  M. Rapé,et al.  The Multiple Layers of Ubiquitin-Dependent Cell Cycle Control , 2009 .

[27]  Ivan Dikic,et al.  Specification of SUMO1- and SUMO2-interacting Motifs* , 2006, Journal of Biological Chemistry.

[28]  Nobuhiro Suzuki,et al.  Specific Recognition of Linear Ubiquitin Chains by NEMO Is Important for NF-κB Activation , 2009, Cell.

[29]  Ivan Dikic,et al.  Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction , 2008, Nature.

[30]  T. Pawson,et al.  Reading protein modifications with interaction domains , 2006, Nature Reviews Molecular Cell Biology.

[31]  T. Mizushima,et al.  Structural Basis for Sorting Mechanism of p62 in Selective Autophagy* , 2008, Journal of Biological Chemistry.

[32]  P. McPherson,et al.  SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination. , 2009, Molecular cell.

[33]  Xiaodong Cheng,et al.  The Ubiquitin Binding Domain ZnF UBP Recognizes the C-Terminal Diglycine Motif of Unanchored Ubiquitin , 2006, Cell.

[34]  M. Petroski.  The Ubiquitin System, Disease and Drug Discovery , 2008 .

[35]  Yuan He,et al.  Ubiquitin binds to and regulates a subset of SH3 domains. , 2007, Molecular cell.

[36]  D. Komander.  The emerging complexity of protein ubiquitination. , 2009, Biochemical Society transactions.

[37]  Keith D Wilkinson,et al.  Polyubiquitin binding and disassembly by deubiquitinating enzymes. , 2009, Chemical reviews.

[38]  K D Wilkinson,et al.  Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. , 1998, Biochemistry.

[39]  Rati Verma,et al.  Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins. , 2008, Journal of molecular biology.

[40]  P. Young,et al.  Structure of S5a bound to monoubiquitin provides a model for polyubiquitin recognition. , 2005, Journal of molecular biology.

[41]  Robert C. Edgar,et al.  MUSCLE: multiple sequence alignment with high accuracy and high throughput. , 2004, Nucleic acids research.

[42]  David Komander,et al.  Breaking the chains: structure and function of the deubiquitinases , 2009, Nature Reviews Molecular Cell Biology.

[43]  J. Cole,et al.  Defining how ubiquitin receptors hHR23a and S5a bind polyubiquitin. , 2007, Journal of molecular biology.

[44]  G. Shaw,et al.  Differential Interaction of the E3 Ligase Parkin with the Proteasomal Subunit S5a and the Endocytic Protein Eps15* , 2009, The Journal of Biological Chemistry.

[45]  Zhijian J. Chen,et al.  TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. , 2004, Molecular cell.

[46]  G. Bjørkøy,et al.  p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy* , 2007, Journal of Biological Chemistry.

[47]  N. Hattori,et al.  Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin‐like domain , 2003, EMBO reports.

[48]  M. Hochstrasser,et al.  Origin and function of ubiquitin-like proteins , 2009, Nature.

[49]  Robert C Piper,et al.  Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex. , 2009, Molecular cell.

[50]  M. Mann,et al.  Ubc9 sumoylation regulates SUMO target discrimination. , 2008, Molecular cell.

[51]  Wim J. N. Meester,et al.  Structure of the Ubiquitin Hydrolase UCH-L3 Complexed with a Suicide Substrate* , 2005, Journal of Biological Chemistry.

[52]  L. Aravind,et al.  Small but versatile: the extraordinary functional and structural diversity of the β-grasp fold , 2007, Biology Direct.

[53]  M. Rapé,et al.  Building ubiquitin chains: E2 enzymes at work , 2009, Nature Reviews Molecular Cell Biology.

[54]  B. Zagrovic,et al.  Conformational selection and induced fit mechanism underlie specificity in noncovalent interactions with ubiquitin , 2009, Proceedings of the National Academy of Sciences.

[55]  Y. Thielmann,et al.  Structural framework of the GABARAP–calreticulin interface – implications for substrate binding to endoplasmic reticulum chaperones , 2009, The FEBS journal.

[56]  S. Gygi,et al.  Extraproteasomal Rpn10 restricts access of the polyubiquitin-binding protein Dsk2 to proteasome. , 2008, Molecular cell.

[57]  Keiji Tanaka,et al.  A ubiquitin ligase complex assembles linear polyubiquitin chains , 2006, The EMBO journal.

[58]  W. Kaelin,et al.  Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. , 1999, Science.

[59]  I. Radhakrishnan,et al.  Structural basis for ubiquitin recognition by SH3 domains. , 2007, Journal of molecular biology.

[60]  M. Rapé,et al.  The multiple layers of ubiquitin-dependent cell cycle control. , 2009, Chemical reviews.

[61]  A. Shilatifard,et al.  The Elongin B Ubiquitin Homology Domain , 1999, The Journal of Biological Chemistry.

[62]  Ziming Zhang,et al.  Small Ubiquitin-like Modifier (SUMO) Recognition of a SUMO Binding Motif , 2005, Journal of Biological Chemistry.

[63]  D. Fushman,et al.  Exploring the linkage dependence of polyubiquitin conformations using molecular modeling. , 2010, Journal of molecular biology.

[64]  Yusuke Sato,et al.  Structural basis for specific recognition of Lys 63‐linked polyubiquitin chains by NZF domains of TAB2 and TAB3 , 2009, The EMBO journal.

[65]  Alfonso Valencia,et al.  Structure-based prediction of the Saccharomyces cerevisiae SH3-ligand interactions. , 2009, Journal of molecular biology.

[66]  J. Yewdell.  Not such a dismal science: the economics of protein synthesis, folding, degradation and antigen processing. , 2001, Trends in cell biology.

[67]  C. Pickart,et al.  Ubiquitin: structures, functions, mechanisms. , 2004, Biochimica et biophysica acta.

[68]  A. Brice,et al.  A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI(3)K–Akt signalling , 2006, Nature Cell Biology.

[69]  M. Glickman,et al.  Together, Rpn10 and Dsk2 can serve as a polyubiquitin chain-length sensor. , 2009, Molecular cell.