Molecular basis of the acetyltransferase activity of MEC-17 towards α-tubulin

Li, Wenjing; Zhong, Chen; Li, Lei; Sun, Bingfa; Wang, Weiyi; Xu, Shutong; Zhang, Tianlong; Wang, Chunguang; Liu, Bao; Ding, Jianping

doi:10.1038/cr.2012.154

Cited by 8 publications

(13 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Basic residues (R69, K98 and K102) lining this groove prove indispensible for catalysis, and could interact with acidic residues adjacent to the substrate lysine, as previously suggested. 18,19,23 The active site architecture and identified catalytic residues are in agreement with the findings in recent publications. 18-20 …”

Section: Resultssupporting

confidence: 91%

“…19,23 However, our further results suggest a more extensive interaction with the substrate that goes beyond the typical recognition of an extended peptide segment, as is common for other acetyltransferases. 17,25 In particular, our biochemical data establish an extensive surface patch, particularly in the β4-β5 hairpin and C-terminal loop, that while distal from the active site is necessary for efficient catalysis.…”

Section: Discussionmentioning

confidence: 53%

“…22 Different groups have proposed that Q58, D157, or D157 and C120 participate as general bases in MEC-17. 19,20,23 Our data cannot currently distinguish among these potential mechanisms. Each of these residues is an appropriate distance from the acetyl-CoA in our crystal structure.…”

Section: Discussionmentioning

confidence: 78%

“…We explored this possibility by testing the ability of MEC-17 to acetylate or bind to a 20-residue α-tubulin peptide centered on K40, consistent with earlier work. 23 Indeed, the peptide proved insufficient for either enzymatic activity or interaction in vitro (Fig. S1).…”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Structural and Functional Characterization of the α-Tubulin Acetyltransferase MEC-17

Davenport

Collins

Chiu

et al. 2014

Journal of Molecular Biology

View full text Add to dashboard Cite

Tubulin protomers undergo an extensive array of post-translational modifications to tailor microtubules to specific tasks. One such modification, the acetylation of lysine-40 of α-tubulin, located in the lumen of microtubules, is associated with stable, long-living microtubule structures. MEC-17 was recently identified as the acetyltransferase that mediates this event. We have determined the crystal structure of the catalytic core of human MEC-17 in complex with its cofactor acetyl-CoA at 1.7 Å resolution. The structure reveals that the MEC-17 core adopts a canonical Gcn5-related N-acetyltransferase (GNAT) fold that is decorated with extensive surface loops. An enzymatic analysis of 33 MEC-17 surface mutants identifies hot-spot residues for catalysis and substrate recognition. A large, evolutionarily conserved hydrophobic surface patch is identified that is critical for enzymatic activity, suggesting that specificity is achieved by interactions with the α-tubulin substrate that extend outside of the modified surface loop. An analysis of MEC-17 mutants in C. elegans shows that enzymatic activity is dispensable for touch sensitivity.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Structural and Functional Characterization of the α-Tubulin Acetyltransferase MEC-17

Davenport

Collins

Chiu

et al. 2014

Journal of Molecular Biology

View full text Add to dashboard Cite

show abstract

“…Of interest, whereas HATs are fully active on histone tail peptides, αTAT1 has no activity on a 19-residue peptide corresponding to the loop where Lys40 resides (Li et al ., 2012). Contrary to histone tails, the H1-S2 loop in α-tubulin is structured, and recognition of the site by αTAT1 may require the proper secondary structure.…”

Section: Resultsmentioning

confidence: 99%

Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure

Howes

Alushin

Shida

et al. 2014

MBoC

161

176

View full text Add to dashboard Cite

show abstract

ChSeq: A database of chameleon sequences

Kinch

Karplus

et al. 2015

Protein Science

View full text Add to dashboard Cite

Chameleon sequences (ChSeqs) refer to sequence strings of identical amino acids that can adopt different conformations in protein structures. Researchers have detected and studied ChSeqs to understand the interplay between local and global interactions in protein structure formation. The different secondary structures adopted by one ChSeq challenge sequence-based secondary structure predictors. With increasing numbers of available Protein Data Bank structures, we here identify a large set of ChSeqs ranging from 6 to 10 residues in length. The homologous ChSeqs discovered highlight the structural plasticity involved in biological function. When compared with previous studies, the set of unrelated ChSeqs found represents an about 20-fold increase in the number of detected sequences, as well as an increase in the longest ChSeq length from 8 to 10 residues. We applied secondary structure predictors on our ChSeqs and found that methods based on a sequence profile outperformed methods based on a single sequence. For the unrelated ChSeqs, the evolutionary information provided by the sequence profile typically allows successful prediction of the prevailing secondary structure adopted in each protein family. Our dataset will facilitate future studies of ChSeqs, as well as interpretations of the interplay between local and nonlocal interactions. A user-friendly web interface for this ChSeq database is available at prodata.swmed.edu/chseq.

show abstract

Molecular basis of the acetyltransferase activity of MEC-17 towards α-tubulin

Cited by 8 publications

References 11 publications

Structural and Functional Characterization of the α-Tubulin Acetyltransferase MEC-17

Structural and Functional Characterization of the α-Tubulin Acetyltransferase MEC-17

Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure

ChSeq: A database of chameleon sequences

Contact Info

Product

Resources

About