ssembly principles of the human R2TP chaperone complex reveal the presence of R2T and R2P complexe

Author(s):Show less -

Seraphim, V, Thiago ; Nano, Nardin ^[1] ; Cheung, Yiu Wing Sunny ^[1] ; Aluksanasuwan, Siripat ^{[1, 2, 3]} ; Colleti, Carolina ^{[4, 1]} ; Mao, Yu-Qian ^[1] ; Bhandari, Vaibhav ^[1] ; Young, Gavin ^[5] ; Holl, Larissa ^[6] ; Phanse, Sadhna ^{[1, 6]} ; Gordiyenko, Yuliya ^[5] ; Southworth, Daniel R. ^[7] ; Robinson, V, Carol ; Thongboonkerd, Visith ^[2] ; Gava, Lisandra M. ^[4] ; Borges, Julio C. ^[8] ; Babu, Mohan ^[6] ; Barbosa, Leandro R. S. ^{[9, 10]} ; Ramos, I, Carlos H. ; Kukura, Philipp ^[11] ; Houry, Walid A. ^{[12, 1]}

Affiliation:Show less -

^[1] Seraphim, Thiago, V, Univ Toronto, Dept Biochem, MaRS Ctr, 661 Univ Ave, West Tower, Room 1612, Toronto, ON M5G 1M1 - Canada

^[2] Mahidol Univ, Fac Med Siriraj Hosp, Med Prote Unit, Off Res & Dev, Bangkok - Thailand

^[3] Mae Fah Luang Univ, Sch Med, Chiang Rai - Thailand

^[4] Univ Fed Sao Carlos, Ctr Biol & Hlth Sci, BR-13560970 Sao Carlos, SP - Brazil

^[5] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ - England

^[6] Seraphim, Thiago, V, Univ Regina, Dept Chem & Biochem, Regina, SK S4S 0A2 - Canada

^[7] Univ Calif San Francisco, Dept Biochem & Biophys, Inst Neurodegenerat Dis, San Francisco, CA 94158 - USA

^[8] Univ Sao Paulo, Sao Carlos Inst Chem, BR-13566590 Sao Carlos, SP - Brazil

^[9] Univ Sao Paulo, Inst Phys, BR-05508090 Sao Paulo, SP - Brazil

^[10] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, BR-13083100 Campinas, SP - Brazil

^[11] Robinson, Carol, V, Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ - England

^[12] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6 - Canada

• Document type: Journal article
• Source: Structure; v. 30, n. 1, p. 156+, JAN 6 2022.
• Web of Science Citations: 0

Abstract

R2TP is a highly conserved chaperone complex formed by two AAA+ ATPases, RUVBL1 and RUVBL2, that associate with PIH1D1 and RPAP3 proteins. R2TP acts in promoting macromolecular complex formation. Here, we establish the principles of R2TP assembly. Three distinct RUVBL1/2-based complexes are identified: R2TP, RUVBL1/2-RPAP3 (R2T), and RUVBL1/2-PIH1D1 (R2P). Interestingly, we find that PIH1D1 does not bind to RUVBL1/RUVBL2 in R2TP and does not function as a nucleotide exchange factor; instead, RPAP3 is found to be the central subunit coordinating R2TP architecture and linking PIH1D1 and RUVBL1/2. We also report that RPAP3 contains an intrinsically disordered N-terminal domain mediating interactions with substrates whose sequences are primarily enriched for Armadillo repeat domains and other helical-type domains. Our work provides a clear and consistent model of R2TP complex structure and gives important insights into how a chaperone machine concerned with assembly of folded proteins into multisubunit complexes might work. (AU)

• FAPESP's process: 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis
• Grantee: Carlos Henrique Inacio Ramos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis
• Grantee: Carlos Henrique Inacio Ramos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/15822-1 - Physicochemical and structural properties of Ionic Liquids and drugs interacting with biologicaly relevant systems.
• Grantee: Leandro Ramos Souza Barbosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/05019-0 - The thermodynamical and structural influence of ionic liquids in biomimetic membrane models
• Grantee: Natália Fernandes de Oliveira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/01603-9 - Determining physical interactions required for R2TP complex assembly using biophysical and biochemical approaches
• Grantee: Carolina Colleti
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• FAPESP's process: 12/01953-9 - Proteins under fibrillation process: a structural and spectroscopic study of the influence of denaturating agents
• Grantee: Leandro Ramos Souza Barbosa
• Support Opportunities: Regular Research Grants