Linked Life Data

16325851

Source:http://linkedlifedata.com/resource/pubmed/id/16325851

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-12-26
pubmed:databankReference
pubmed:abstractText
Autophagy is an evolutionarily conserved pathway in which the cytoplasm and organelles are engulfed within double-membrane vesicles, termed autophagosomes, for the turnover and recycling of these cellular constituents. The yeast Atg8 and its human orthologs, such as LC3 and GABARAP, have a unique feature as they conjugate covalently to phospholipids, differing from ubiquitin and other ubiquitin-like modifiers that attach only to protein substrates. The lipidated Atg8 and LC3 localize to autophagosomal membranes and play indispensable roles for maturation of autophagosomes. Upon completion of autophagosome formation, some populations of lipidated Atg8 and LC3 are delipidated for recycling. Atg4b, a specific protease for LC3 and GABARAP, catalyzes the processing reaction of LC3 and GABARAP precursors to mature forms and de-conjugating reaction of the modifiers from phospholipids. Atg4b is a unique enzyme whose primary structure differs from that of any other proteases that function as processing and/or de-conjugating enzymes of ubiquitin and ubiquitin-like modifiers. However, the tertiary structures of the substrates considerably resemble that of ubiquitin except for the N-terminal additional domain. Here we determined the crystal structure of human Atg4b by X-ray crystallography at 2.0 A resolution, and show that Atg4b is a cysteine protease whose active catalytic triad site consists of Cys74, His280 and Asp278. The structure is comprised of a left lobe and a small right lobe, designated the "protease domain" and the "auxiliary domain", respectively. Whereas the protease domain structure of Atg4b matches that of papain superfamily cysteine proteinases, the auxiliary domain contains a unique structure with yet-unknown function. We propose that the R229 and W142 residues in Atg4b are specifically essential for recognition of substrates and catalysis of both precursor processing and de-conjugation of phospholipids.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
355
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
612-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
The crystal structure of human Atg4b, a processing and de-conjugating enzyme for autophagosome-forming modifiers.
pubmed:affiliation
Department of Biotechnology, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya 464-8603, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't