Asparagine β-hydroxylation stabilizes the ankyrin repeat domain fold

被引：49

作者：

Kelly, Leanne ^{[2
,3
]}

McDonough, Michael A. ^{[2
,3
]}

Coleman, Mathew L. ^{[1
]}

Ratcliffe, Peter J. ^{[1
]}

Schofield, Christopher J. ^{[1
]}

机构：

[1] Univ Oxford, Oxford OX3 7BN, England

[2] Univ Oxford, Chem Res Lab, Oxford OX1 3TA, England

[3] Univ Oxford, Oxford Ctr Integrat Syst Biol, Oxford OX1 3TA, England

来源：

MOLECULAR BIOSYSTEMS | 2009年 / 5卷 / 01期

基金：

英国惠康基金;

关键词：

HYPOXIA-INDUCIBLE-FACTOR; INHIBITING-HIF FIH; CONFORMATIONAL STABILITY; STRUCTURAL BASIS; PROTEIN; MECHANISM; DESIGN; RECOGNITION; SOFTWARE; COLLAGEN;

D O I：

10.1039/b815271c

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ankyrin repeats (ARs) are one of the most common structural motifs among eukaryotic proteins. Recent analyses have shown that factor inhibiting hypoxia-inducible factor (FIH) catalyses the hydroxylation of highly conserved Asn-residues within ankyrin repeat domains (ARDs). However, the effect of Asn-hydroxylation on ARD structure is unknown. Supporting the proposal that FIH-mediated ARD hydroxylation is ubiquitous we report that consensus ARD proteins are FIH substrates both in vitro and in vivo. X-ray diffraction analyses revealed that hydroxylation does not alter the archetypical ARD conformation in the crystalline state. However, other biophysical analyses revealed that hydroxylation significantly stabilizes the ARD fold in solution. We propose that intracellular protein hydroxylation is much more common than previously thought and that one of its roles is stabilization of localized regions of ARD folds.

引用

页码：52 / 58

页数：7

共 34 条

[1] Designing repeat proteins:: Well-expressed, soluble and stable proteins from combinatorial libraries of consensus ankyrin repeat proteins [J].

Binz, HK ;

Stumpp, MT ;

Forrer, P ;

Amstutz, P ;

Plückthun, A .

JOURNAL OF MOLECULAR BIOLOGY, 2003, 332 (02) :489-503

[2] Conformational stability of collagen relies on a stereoelectronic effect [J].

Bretscher, LE ;

Jenkins, CL ;

Taylor, KM ;

DeRider, ML ;

Raines, RT .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (04) :777-778

[3] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[4] Design and characterization of a hyperstable p16INK4a that restores Cdk4 binding activity when combined with oncogenic mutations [J].

Cammett, TJ ;

Luo, L ;

Peng, ZY .

JOURNAL OF MOLECULAR BIOLOGY, 2003, 327 (01) :285-297

[5] Posttranslational hydroxylation of ankyrin repeats in IκB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH) [J].

Cockman, Matthew E. ;

Lancaster, David E. ;

Stolze, Ineke P. ;

Hewitson, Kirsty S. ;

McDonough, Michael A. ;

Coleman, Mathew L. ;

Coles, Charlotte H. ;

Yu, Xiaohong ;

Hay, Ronald T. ;

Ley, Steven C. ;

Pugh, Christopher W. ;

Oldham, Neil J. ;

Masson, Norma ;

Schofield, Christopher J. ;

Ratcliffe, Peter J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (40) :14767-14772

[6] Asparaginyl hydroxylation of the notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor [J].

Coleman, Mathew L. ;

McDonough, Michael A. ;

Hewitson, Kirsty S. ;

Coles, Charlotte ;

Mecinovic, Jasmin ;

Edelmann, Mariola ;

Cook, Kristina M. ;

Cockman, Matthew E. ;

Lancaster, David E. ;

Kessler, Benedikt M. ;

Oldham, Neil J. ;

Ratcliffe, Peter J. ;

Schofield, Christopher J. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (33) :24027-24038

[7] Structural basis for Hif-1α/CBP recognition in the cellular hypoxic response [J].

Dames, SA ;

Martinez-Yamout, M ;

De Guzman, RN ;

Dyson, HJ ;

Wright, PE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (08) :5271-5276

[8] Absence of post-translational aspartyl β-hydroxylation of epidermal growth factor domains in mice leads to developmental defects and an increased incidence of intestinal neoplasia [J].

Dinchuk, JE ;

Focht, RJ ;

Kelley, JA ;

Henderson, NL ;

Zolotarjova, NI ;

Wynn, R ;

Neff, NT ;

Link, J ;

Huber, RM ;

Burn, TC ;

Rupar, MJ ;

Cunningham, MR ;

Selling, BH ;

Ma, JH ;

Stern, AA ;

Hollis, GF ;

Stein, RB ;

Friedman, PA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (15) :12970-12977

[9] Studies on the activity of the hypoxia-inducible-factor hydroxylases using an oxygen consumption assay [J].

Ehrismann, Dominic ;

Flashman, Emily ;

Genn, David N. ;

Mathioudakis, Nicolas ;

Hewitson, Kirsty S. ;

Ratcliffe, Peter J. ;

Schofield, Christopher J. .

BIOCHEMICAL JOURNAL, 2007, 401 :227-234

[10] Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1α [J].

Elkins, JM ;

Hewitson, KS ;

McNeill, LA ;

Seibel, JF ;

Schlemminger, I ;

Pugh, CW ;

Ratcliffe, PJ ;

Schofield, CJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1802-1806

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