4AIF

AIP TPR domain in complex with human Hsp90 peptide

Summary for 4AIF

• Entry DOI: 10.2210/pdb4aif/pdb
• Related: 1BYQ 1OSF 1UY6 1UY7 1UY8 1UY9 1UYC 1UYD 1UYE 1UYF 1UYG 1UYH 1UYI 1UYK 1UYL 1YC1 1YC3 1YC4 1YER 1YES 1YET 2BSM 2BT0 2BUG 2BYH 2BYI 2BZ5 2C2L 2CCS 2CCT 2CCU 2CDD 2FWY 2FWZ 2JJC 2UWD 2VCI 2VCJ 2WI1 2WI2 2WI3 2WI4 2WI5 2WI6 2WI7 2XAB 2XDK 2XDL 2XDS 2XDU 2XDX 2XHR 2XHT 2XHX 2XJG 2XJJ 2XJX 2XK2 2YE2 2YE3 2YE4 2YE5 2YE6 2YE7 2YE8 2YE9 2YEA 2YEB 2YEC 2YED 2YEE 2YEF 2YEG 2YEH 2YEI 2YEJ 2YI0 2YI5 2YI6 2YI7 2YJW 2YJX 2YK2 2YK9 2YKB 2YKC 2YKE 2YKI 2YKJ
• Descriptor: AH RECEPTOR-INTERACTING PROTEIN, HEAT SHOCK PROTEIN HSP 90-ALPHA, SULFATE ION, ... (4 entities in total)
• Functional Keywords: signaling protein-peptide complex, aryl hydrocarbon receptor, signaling protein/peptide
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: O00170 P07900
• Total number of polymer chains: 4
• Total formula weight: 34727.41

Authors

Morgan, R.M.L.,Roe, S.M.,Pearl, L.H.,Prodromou, C. (deposition date: 2012-02-09, release date: 2013-01-23, Last modification date: 2024-05-01)

Primary citation

Morgan, R.M.,Hernandez-Ramirez, L.C.,Trivellin, G.,Zhou, L.,Roe, S.M.,Korbonits, M.,Prodromou, C.
Structure of the Tpr Domain of Aip: Lack of Client Protein Interaction with the C-Terminal Alpha-7 Helix of the Tpr Domain of Aip is Sufficient for Pituitary Adenoma Predisposition.
Plos One, 7:53339-, 2012

PubMed Abstract: Mutations of the aryl hydrocarbon receptor interacting protein (AIP) have been associated with familial isolated pituitary adenomas predisposing to young-onset acromegaly and gigantism. The precise tumorigenic mechanism is not well understood as AIP interacts with a large number of independent proteins as well as three chaperone systems, HSP90, HSP70 and TOMM20. We have determined the structure of the TPR domain of AIP at high resolution, which has allowed a detailed analysis of how disease-associated mutations impact on the structural integrity of the TPR domain. A subset of C-terminal α-7 helix (Cα-7h) mutations, R304* (nonsense mutation), R304Q, Q307* and R325Q, a known site for AhR and PDE4A5 client-protein interaction, occur beyond those that interact with the conserved MEEVD and EDDVE sequences of HSP90 and TOMM20. These C-terminal AIP mutations appear to only disrupt client-protein binding to the Cα-7h, while chaperone binding remains unaffected, suggesting that failure of client-protein interaction with the Cα-7h is sufficient to predispose to pituitary adenoma. We have also identified a molecular switch in the AIP TPR-domain that allows recognition of both the conserved HSP90 motif, MEEVD, and the equivalent sequence (EDDVE) of TOMM20.

PubMed: 23300914
DOI: 10.1371/JOURNAL.PONE.0053339

Experimental method

X-RAY DIFFRACTION (2.006 Å)