TY - JOUR
T1 - The structure of the 26S proteasome subunit Rpn2 reveals its PC repeat domain as a closed toroid of two concentric α-helical rings
AU - He, Jun
AU - Kulkarni, Kiran
AU - Da Fonseca, Paula C.A.
AU - Krutauz, Dasha
AU - Glickman, Michael H.
AU - Barford, David
AU - Morris, Edward P.
N1 - Funding Information: The work is supported by an ICR studentship (to J.H.) and a CR-UK Programme grant (to D.B.). We thank Dr. Nora Cronin and the staff at ESRF (beam line ID23) for help with data collection.
PY - 2012/3/7
Y1 - 2012/3/7
N2 - The 26S proteasome proteolyses ubiquitylated proteins and is assembled from a 20S proteolytic core and two 19S regulatory particles (19S-RP). The 19S-RP scaffolding subunits Rpn1 and Rpn2 function to engage ubiquitin receptors. Rpn1 and Rpn2 are characterized by eleven tandem copies of a 35-40 amino acid repeat motif termed the proteasome/cyclosome (PC) repeat. Here, we reveal that the eleven PC repeats of Rpn2 form a closed toroidal structure incorporating two concentric rings of α helices encircling two axial α helices. A rod-like N-terminal domain consisting of 17 stacked α helices and a globular C-terminal domain emerge from one face of the toroid. Rpn13, an ubiquitin receptor, binds to the C-terminal 20 residues of Rpn2. Rpn1 adopts a similar conformation to Rpn2 but differs in the orientation of its rod-like N-terminal domain. These findings have implications for understanding how 19S-RPs recognize, unfold, and deliver ubiquitylated substrates to the 20S core.
AB - The 26S proteasome proteolyses ubiquitylated proteins and is assembled from a 20S proteolytic core and two 19S regulatory particles (19S-RP). The 19S-RP scaffolding subunits Rpn1 and Rpn2 function to engage ubiquitin receptors. Rpn1 and Rpn2 are characterized by eleven tandem copies of a 35-40 amino acid repeat motif termed the proteasome/cyclosome (PC) repeat. Here, we reveal that the eleven PC repeats of Rpn2 form a closed toroidal structure incorporating two concentric rings of α helices encircling two axial α helices. A rod-like N-terminal domain consisting of 17 stacked α helices and a globular C-terminal domain emerge from one face of the toroid. Rpn13, an ubiquitin receptor, binds to the C-terminal 20 residues of Rpn2. Rpn1 adopts a similar conformation to Rpn2 but differs in the orientation of its rod-like N-terminal domain. These findings have implications for understanding how 19S-RPs recognize, unfold, and deliver ubiquitylated substrates to the 20S core.
UR - http://www.scopus.com/inward/record.url?scp=84857935771&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.str.2011.12.015
DO - https://doi.org/10.1016/j.str.2011.12.015
M3 - مقالة
SN - 0969-2126
VL - 20
SP - 513
EP - 521
JO - Structure
JF - Structure
IS - 3
ER -