Insights into the architecture of the replicative helicase from the structure of an archaeal MCM homolog.
The minichromosome maintenance (MCM) proteins, members of the AAA+ (ATPase associated with diverse cellular activities) superfamily, are believed to constitute the replicative helicase in eukaryotic and archaeal species. Here, we present the 1.9 A resolution crystal structure of a monomeric MCM homolog from Methanopyrus kandleri, the first crystallographic structure of a full-length MCM. We also present an 18 A cryo-electron microscopy reconstruction of the hexameric MCM from Methanothermobacter thermautotrophicus, and fit the atomic resolution crystal structure into the reconstruction in order to generate an atomic model for the oligomeric assembly. These structural data reveal a distinct active site topology consisting of a unique arrangement of critical determinants. The structures also provide a molecular framework for understanding the functional contributions of trans-acting elements that facilitate intersubunit crosstalk in response to DNA binding and ATP hydrolysis.
Bae
Brian
B
Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave, Urbana, IL 61801, USA.
Chen
Yi-Hsing
YH
Costa
Alessandro
A
Onesti
Silvia
S
Brunzelle
Joseph S
JS
Lin
Yuyen
Y
Cann
Isaac K O
IK
Nair
Satish K
SK
D000595:Amino Acid Sequence; D000818:Animals; D001105:Archaea / Q000201:enzymology; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D004265:DNA Helicases / Q000737:chemistry* / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology; D005057:Eukaryotic Cells / Q000201:enzymology; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D055503:Protein Multimerization; D017386:Sequence Homology, Amino Acid
D019843:Archaeal Proteins; D009687:Nuclear Proteins; D004265:DNA Helicases; D064111:Minichromosome Maintenance Complex Component 2; C403162:MCM protein, Methanobacterium thermoautotrophicum