Interaction of the TAZ1 Domain of the CREB-Binding Protein with the Activation Domain of CITED2: REGULATION BY COMPETITION BETWEEN INTRINSICALLY UNSTRUCTURED LIGANDS FOR NON-IDENTICAL BINDING SITES Export

@article{citeulike:3024807, abstract = {The TAZ1 domain of the homologous transcriptional coactivators CREB-binding protein (CBP) and p300 forms a complex with CITED2 (CBP/p300-interacting transactivator with ED-rich tail), inhibiting the activity of the hypoxia inducible factor (HIF-1{alpha}) and thereby attenuating the cellular response to low tissue oxygen concentration. We report the NMR structure of the CBP TAZ1 domain bound to the activation domain of CIT-ED2. The structure of TAZ1, consisting of four {alpha}-helices ({alpha}1-{alpha}4) stabilized by three zinc atoms, is very similar in the CITED2 and HIF-1{alpha} complexes. The activation domain of CITED2 is unstructured when free and folds upon binding, forming a helix (termed {alpha}A) and an extended structure that wraps around TAZ1. The CITED2 {alpha}A helix packs in the TAZ1 {alpha}1/{alpha}4 interface, a site that forms weak interactions with the poorly defined aminoterminal {alpha}-helix of HIF-1{alpha}. CITED2 and HIF-1{alpha} both contain a four residue motif, LP(E/Q)L, which binds in the TAZ1 {alpha}1/{alpha}2/{alpha}3 junction in each complex. The carboxyl-terminal region of CITED2 forms an extended structure with hydrophobic contacts in the TAZ1 {alpha}1/{alpha}3 interface in the site occupied by the HIF-1{alpha} {alpha}B helix. CITED2 does not bind at all to the TAZ1 site occupied by the HIF-1{alpha} carboxyl-terminal helix. The HIF-1{alpha} and CITED2 domains utilize partly overlapping surfaces of TAZ1 to achieve high affinity binding and to compete effectively with each other for interaction with CBP/p300; CITED2 and HIF-1{alpha} use these binding sites differently to maintain similar binding affinities in order to displace each other in a feedback loop during the hypoxic response. 10.1074/jbc.M310348200}, author = {De Guzman, Roberto N. and Martinez-Yamout, Maria A. and Dyson, Jane H. and Wright, Peter E.}, citeulike-article-id = {3024807}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M310348200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/279/4/3042}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/14594809}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=14594809}, day = {23}, doi = {10.1074/jbc.M310348200}, journal = {J. Biol. Chem.}, keywords = {cbp, ch1, cited2, nmr-structure}, month = {January}, number = {4}, pages = {3042--3049}, posted-at = {2008-07-21 17:03:49}, priority = {2}, title = {Interaction of the TAZ1 Domain of the CREB-Binding Protein with the Activation Domain of CITED2: REGULATION BY COMPETITION BETWEEN INTRINSICALLY UNSTRUCTURED LIGANDS FOR NON-IDENTICAL BINDING SITES}, url = {http://dx.doi.org/10.1074/jbc.M310348200}, volume = {279}, year = {2004} }

TY - JOUR ID - citeulike:3024807 L3 - citeulike-article-id:3024807 N2 - The TAZ1 domain of the homologous transcriptional coactivators CREB-binding protein (CBP) and p300 forms a complex with CITED2 (CBP/p300-interacting transactivator with ED-rich tail), inhibiting the activity of the hypoxia inducible factor (HIF-1{alpha}) and thereby attenuating the cellular response to low tissue oxygen concentration. We report the NMR structure of the CBP TAZ1 domain bound to the activation domain of CIT-ED2. The structure of TAZ1, consisting of four {alpha}-helices ({alpha}1-{alpha}4) stabilized by three zinc atoms, is very similar in the CITED2 and HIF-1{alpha} complexes. The activation domain of CITED2 is unstructured when free and folds upon binding, forming a helix (termed {alpha}A) and an extended structure that wraps around TAZ1. The CITED2 {alpha}A helix packs in the TAZ1 {alpha}1/{alpha}4 interface, a site that forms weak interactions with the poorly defined aminoterminal {alpha}-helix of HIF-1{alpha}. CITED2 and HIF-1{alpha} both contain a four residue motif, LP(E/Q)L, which binds in the TAZ1 {alpha}1/{alpha}2/{alpha}3 junction in each complex. The carboxyl-terminal region of CITED2 forms an extended structure with hydrophobic contacts in the TAZ1 {alpha}1/{alpha}3 interface in the site occupied by the HIF-1{alpha} {alpha}B helix. CITED2 does not bind at all to the TAZ1 site occupied by the HIF-1{alpha} carboxyl-terminal helix. The HIF-1{alpha} and CITED2 domains utilize partly overlapping surfaces of TAZ1 to achieve high affinity binding and to compete effectively with each other for interaction with CBP/p300; CITED2 and HIF-1{alpha} use these binding sites differently to maintain similar binding affinities in order to displace each other in a feedback loop during the hypoxic response. 10.1074/jbc.M310348200 IS - 4 JF - J. Biol. Chem. EP - 3049 TI - Interaction of the TAZ1 Domain of the CREB-Binding Protein with the Activation Domain of CITED2: REGULATION BY COMPETITION BETWEEN INTRINSICALLY UNSTRUCTURED LIGANDS FOR NON-IDENTICAL BINDING SITES VL - 279 SP - 3042 KW - cbp KW - ch1 KW - cited2 KW - nmr-structure AU - De Guzman, Roberto AU - Martinez-Yamout, Maria AU - Dyson, Jane AU - Wright, Peter PY - 2004/01/23/ UR - http://dx.doi.org/10.1074/jbc.M310348200 ER -