Structural biology of the TGFβ family

Specificity, versatility, and control of TGF-β family signaling

(2019) Rik Derynck et al.   Science Signaling

Crystal structure of the WFIKKN2 follistatin domain reveals insight into how it inhibits growth differentiation factor 8 (GDF8) and GDF11

(2019) Jason C. McCoy et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Bis-Heteroaryl Pyrazoles: Identification of Orally Bioavailable Inhibitors of Activin Receptor-Like Kinase-2 (R206H)

(2019) Katsuhiko Sekimata et al.   CHEMICAL & PHARMACEUTICAL BULLETIN

Structural characterization of an activin class ternary receptor complex reveals a third paradigm for receptor specificity

(2019) Erich J. Goebel et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Heterobicyclic inhibitors of transforming growth factor beta receptor I (TGFβRI)

(2018) Lalgudi S. Harikrishnan et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2

(2018) Eleanor Williams et al.   BONE

Tolloid cleavage activates latent GDF8 by priming the pro‐complex for dissociation

(2018) Viet Q Le et al.   EMBO JOURNAL

Structure of the human myostatin precursor and determinants of growth factor latency

(2018) Thomas R Cotton et al.   EMBO JOURNAL

Molecular characterization of latent GDF8 reveals mechanisms of activation

(2018) Ryan G. Walker et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Hydrophobic patches on SMAD2 and SMAD3 determine selective binding to cofactors

(2018) Ken-ichi Miyazono et al.   Science Signaling

TGF-β uses a novel mode of receptor activation to phosphorylate SMAD1/5 and induce epithelial-to-mesenchymal transition

(2018) Anassuya Ramachandran et al.   eLife

Hydrophobic patches on SMAD2 and SMAD3 determine selective binding to cofactors

(2018) Ken-ichi Miyazono et al.   Science Signaling

Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure–Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept

(2018) Liam Hudson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural basis for receptor-regulated SMAD recognition by MAN1

(2018) Ken-ichi Miyazono et al.   NUCLEIC ACIDS RESEARCH

Structural basis of latent TGF-β1 presentation and activation by GARP on human regulatory T cells

(2018) Stéphanie Liénart et al.   SCIENCE

Discovery of 4-Azaindole Inhibitors of TGFβRI as Immuno-oncology Agents

(2018) Yong Zhang et al.   ACS Medicinal Chemistry Letters

Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2

(2017) Emma-Ruoqi Xu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Prodomain–growth factor swapping in the structure of pro-TGF-β1

(2017) Bo Zhao et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Role of GARP in the activation of latent TGF-β1

(2017) Julie Stockis et al.   Molecular BioSystems

Force interacts with macromolecular structure in activation of TGF-β

(2017) Xianchi Dong et al.   NATURE

Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8

(2017) Julie Stockis et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors

(2017) Pau Martin-Malpartida et al.   Nature Communications

Structure of Gremlin-1 and analysis of its interaction with BMP-2

(2016) M. Ki onaite et al.   BIOCHEMICAL JOURNAL

Structural insights into BMP receptors: Specificity, activation and inhibition

(2016) David Yadin et al.   CYTOKINE & GROWTH FACTOR REVIEWS

Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody

(2016) James R. Apgar et al.   mAbs

Biological activity and in vivo half-life of pro-activin A in male rats

(2016) Katharine E. Johnson et al.   MOLECULAR AND CELLULAR ENDOCRINOLOGY

Identification and optimisation of a series of N-(4-anilino-2-pyridyl)acetamide activin receptor-like kinase 1 (ALK1) inhibitors

(2016) Frederick W. Goldberg et al.   MedChemComm

Transcriptional Control by the SMADs

(2016) Caroline S. Hill   Cold Spring Harbor Perspectives in Biology

Structural Basis of Intracellular TGF-β Signaling: Receptors and Smads

(2016) Apirat Chaikuad et al.   Cold Spring Harbor Perspectives in Biology

Structural Biology and Evolution of the TGF-β Family

(2016) Andrew P. Hinck et al.   Cold Spring Harbor Perspectives in Biology

Signaling Receptors for TGF-β Family Members

(2016) Carl-Henrik Heldin et al.   Cold Spring Harbor Perspectives in Biology

TGF-β Signaling from Receptors to Smads

(2016) Akiko Hata et al.   Cold Spring Harbor Perspectives in Biology

Structure and activation of pro-activin A

(2016) Xuelu Wang et al.   Nature Communications

Structure of Gremlin-2 in Complex with GDF5 Gives Insight into DAN-Family-Mediated BMP Antagonism

(2016) Kristof Nolan et al.   Cell Reports

Crystal structures of apo and inhibitor-bound TGFβR2 kinase domain: insights into TGFβR isoform selectivity

(2016) Andrew J. Tebben et al.   Acta Crystallographica Section D-Structural Biology

Crystal structure of human GDF11

(2016) Anil K. Padyana et al.   Acta Crystallographica Section F-Structural Biology Communications

A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis

(2015) Georgina Kerr et al.   ANGIOGENESIS

GDF-5 can act as a context-dependent BMP-2 antagonist

(2015) Uwe Klammert et al.   BMC BIOLOGY

Alternative Binding Modes Identified for Growth and Differentiation Factor-associated Serum Protein (GASP) Family Antagonism of Myostatin

(2015) Ryan G. Walker et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Adaptive Immunity to Leukemia Is Inhibited by Cross-Reactive Induced Regulatory T Cells

(2015) Luke S. Manlove et al.   JOURNAL OF IMMUNOLOGY

Structural basis for the Smad5 MH1 domain to recognize different DNA sequences

(2015) Nan Chai et al.   NUCLEIC ACIDS RESEARCH

Structure of bone morphogenetic protein 9 procomplex

(2015) Li-Zhi Mi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo

(2015) Julia Cuende et al.   Science Translational Medicine

ACVR1 R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A

(2015) Sarah J. Hatsell et al.   Science Translational Medicine

Biological Activity Differences between TGF-β1 and TGF-β3 Correlate with Differences in the Rigidity and Arrangement of Their Component Monomers

(2014) Tao Huang et al.   BIOCHEMISTRY

Integrins αvβ5 and αvβ3 promote latent TGF-β1 activation by human cardiac fibroblast contraction

(2014) Vincent Sarrazy et al.   CARDIOVASCULAR RESEARCH

Regulation of Bone Morphogenetic Protein 9 (BMP9) by Redox-dependent Proteolysis

(2014) Zhenquan Wei et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Small Molecules Dorsomorphin and LDN-193189 Inhibit Myostatin/GDF8 Signaling and Promote Functional Myoblast Differentiation

(2014) Daniel Horbelt et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structure–Activity Relationship of 3,5-Diaryl-2-aminopyridine ALK2 Inhibitors Reveals Unaltered Binding Affinity for Fibrodysplasia Ossificans Progressiva Causing Mutants

(2014) Agustin H. Mohedas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Selection of Fragments for Kinase Inhibitor Design: Decoration Is Key

(2014) Paul Czodrowski et al.   JOURNAL OF MEDICINAL CHEMISTRY

Nanoscale structure of the BMP antagonist chordin supports cooperative BMP binding

(2014) H. Troilo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The DAN family: Modulators of TGF-β signaling and beyond

(2014) Kristof Nolan et al.   PROTEIN SCIENCE

Activins bind and signal via bone morphogenetic protein receptor type II (BMPR2) in immortalized gonadotrope-like cells

(2013) Carlis A. Rejon et al.   CELLULAR SIGNALLING

The Clip-Segment of the von Willebrand Domain 1 of the BMP Modulator Protein Crossveinless 2 Is Preformed

(2013) Juliane Fiebig et al.   MOLECULES

A New Class of Small Molecule Inhibitor of BMP Signaling

(2013) Caroline E. Sanvitale et al.   PLoS One

Structure of Protein Related to Dan and Cerberus: Insights into the Mechanism of Bone Morphogenetic Protein Antagonism

(2013) Kristof Nolan et al.   STRUCTURE

Structure of the Alk1 Extracellular Domain and Characterization of Its Bone Morphogenetic Protein (BMP) Binding Properties

(2012) Pardeep Mahlawat et al.   BIOCHEMISTRY

Structure of the Bone Morphogenetic Protein Receptor ALK2 and Implications for Fibrodysplasia Ossificans Progressiva

(2012) Apirat Chaikuad et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Specificity and Structure of a High Affinity Activin Receptor-like Kinase 1 (ALK1) Signaling Complex

(2012) Sharon A. Townson et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

GARP regulates the bioavailability and activation of TGFβ

(2012) Rui Wang et al.   MOLECULAR BIOLOGY OF THE CELL

TGFβ signalling in context

(2012) Joan Massagué   NATURE REVIEWS MOLECULAR CELL BIOLOGY

GASP/WFIKKN Proteins: Evolutionary Aspects of Their Functions

(2012) Olivier Monestier et al.   PLoS One

Structural basis for specificity of TGFβ family receptor small molecule inhibitors

(2011) Abiodun A. Ogunjimi et al.   CELLULAR SIGNALLING

Prodomains regulate the synthesis, extracellular localisation and activity of TGF-β superfamily ligands

(2011) Craig A. Harrison et al.   GROWTH FACTORS

Structure of Myostatin·Follistatin-like 3

(2011) Jennifer N. Cash et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The T?R-I Pre-Helix Extension Is Structurally Ordered in the Unbound Form and Its Flanking Prolines Are Essential for Binding

(2011) Jorge E. Zuniga et al.   JOURNAL OF MOLECULAR BIOLOGY

Latent TGF-β structure and activation

(2011) Minlong Shi et al.   NATURE

Ternary Complex of Transforming Growth Factor-β1 Reveals Isoform-specific Ligand Recognition and Receptor Recruitment in the Superfamily

(2010) Sergei Radaev et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Design, Synthesis, and Evaluation of Indolinones as Inhibitors of the Transforming Growth Factor β Receptor I (TGFβRI)

(2010) Gerald J. Roth et al.   JOURNAL OF MEDICINAL CHEMISTRY

NMR structure of the Wnt modulator protein Sclerostin

(2009) Stella E. Weidauer et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

TβR-II Discriminates the High- and Low-Affinity TGF-β Isoforms via Two Hydrogen-Bonded Ion Pairs†

(2009) Jason Baardsnes et al.   BIOCHEMISTRY

Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors

(2009) F. Gellibert et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Pyrazolone based TGFβR1 kinase inhibitors

(2009) Kevin Guckian et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Receptor oligomerization and beyond: a case study in bone morphogenetic proteins

(2009) Kai Heinecke et al.   BMC BIOLOGY

The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding

(2009) Jennifer N Cash et al.   EMBO JOURNAL

Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5–type I receptor specificity

(2009) Alexander Kotzsch et al.   EMBO JOURNAL

Membrane protein GARP is a receptor for latent TGF-β on the surface of activated human Treg

(2009) Julie Stockis et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Characterization of the Structural Features and Interactions of Sclerostin

(2009) Vaclav Veverka et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Rapid Generation of a High Quality Lead for Transforming Growth Factor-β (TGF-β) Type I Receptor (ALK5)†

(2009) Frederick W. Goldberg et al.   JOURNAL OF MEDICINAL CHEMISTRY

GARP (LRRC32) is essential for the surface expression of latent TGF-  on platelets and activated FOXP3+ regulatory T cells

(2009) D. Q. Tran et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Solution Structure of BMPR-IA Reveals a Local Disorder-to-Order Transition upon BMP-2 Binding†‡

(2008) Jochen Klages et al.   BIOCHEMISTRY

2-Aminoimidazoles inhibitors of TGF-β receptor 1

(2008) Dominique Bonafoux et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Phospho-control of TGF-β superfamily signaling

(2008) Katharine H Wrighton et al.   CELL RESEARCH

Crystal Structure Analysis Reveals How the Chordin Family Member Crossveinless 2 Blocks BMP-2 Receptor Binding

(2008) Jin-li Zhang et al.   DEVELOPMENTAL CELL

The Structure of FSTL3·Activin A Complex

(2008) Robin Stamler et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Both WFIKKN1 and WFIKKN2 Have High Affinity for Growth and Differentiation Factors 8 and 11

(2008) Katalin Kondás et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength

(2008) Xiaodong Li et al.   JOURNAL OF BONE AND MINERAL RESEARCH

Cooperative Assembly of TGF-β Superfamily Signaling Complexes Is Mediated by Two Disparate Mechanisms and Distinct Modes of Receptor Binding

(2008) Jay Groppe et al.   MOLECULAR CELL