Structure of a functional IGF2R fragment determined from the anomalous scattering of sulfur

Brown, James; Esnouf, Robert; Jones, Margaret; Linnell, Jane; Harlos, K.; Hassan, A. Bassim; Jones, Emma

doi:10.1093/emboj/21.5.1054

Cited by 93 publications

(92 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The main structural domains of IGF-IIR that account for affinity and specificity are domains 11 and 13, with key hydrophobic residues (patch1) on domain 11 accounting for the main contribution of affinity [30][31][32].…”

Section: Insulin-like Growth Factor Ligands Receptors and Binding Pmentioning

confidence: 99%

Insulin‐like growth factor ligands, receptors, and binding proteins in cancer

Foulstone

Prince

Zaccheo

et al. 2005

The Journal of Pathology

229

179

View full text Add to dashboard Cite

This review aims to summarize experimental evidence supporting the role of the insulinlike growth factor (IGF) signalling system in the progression, maintenance, and treatment of cancer. These data implicate the IGF system as an important modifier of cancer cell proliferation, survival, growth, and treatment sensitivity. The role of the IGF system in cancer should be examined in the context of the extra-cellular and intra-cellular signalling networks, in particular: phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt/PKB), mammalian target of rapamycin (mTOR), and forkhead transcription factors (FOXO). This review highlights evidence derived from molecular structure and functional genetics with respect to how the extra-cellular components of the IGF system function normally, and their subsequent modifications in cancer. The therapeutic relevance of the research evidence described is also addressed, as the challenge is to apply this knowledge to human health.

show abstract

Section: Insulin-like Growth Factor Ligands Receptors and Binding Pmentioning

confidence: 99%

Insulin‐like growth factor ligands, receptors, and binding proteins in cancer

Foulstone

Prince

Zaccheo

et al. 2005

The Journal of Pathology

229

179

View full text Add to dashboard Cite

show abstract

“…The best characterized of these is the mitogen insulin-like growth factor 2 (IGF2). It binds to a M6P-independent, high-affinity receptor binding site 7 that evolved with the appearance of Therian mammals. 8 Bound IGF2 is then internalized and transported to the lysosomes where it is degraded; M6P/IGF2R is subsequently recycled back to the membrane.…”

mentioning

confidence: 99%

Tissue-Specific Inactivation of Murine M6P/IGF2R

Wylie

Pulford

McVie‐Wylie

et al. 2003

The American Journal of Pathology

View full text Add to dashboard Cite

The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and T cell-mediated immunity. M6P/IGF2R is an imprinted gene in mice with expression only from the maternal allele. Complete knockout of this gene causes neonatal lethality, thus preventing analysis of its multifunctional role postnatally. To help elucidate the biological functions of M6P/IGF2R in adulthood, we generated both complete and tissue-specific M6P/IGF2R knockout mice using the Cre/loxP system. We confirm that complete M6P/IGF2R knockout results in fetal overgrowth and neonatal lethality. In contrast, tissue-specific inactivation of this gene in either the liver or skeletal and cardiac muscle gives rise to viable animals with no obvious phenotype. The successful creation of viable tissue-specific M6P/IGF2R knockout mouse models will now allow for detailed analysis of receptor function in a number of cellular processes including brain development, carcinogenesis, lysosomal trafficking, and T cell-mediated immunity. Both the 275-kd cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) and the 46-kd cation-dependent mannose 6-phosphate receptor (M6PR) function in the intracellular trafficking of lysosomal enzymes.

show abstract

“…Most of the sulfur SAD data have been collected on tunable synchrotron beamlines in order to make use of the appreciably larger f″ of sulfur at longer wavelengths in the range between 1.7 -2.5 Å [24][25][26][27][28][29][30] although Cu Kα is also feasible for sulfur SAD phasing [31][32][33]. Both copper and chromium anode wavelengths (1.54 and 2.29 Å) have been increasingly employed for the same purpose in lab X-ray sources with success [34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Lab Source Anomalous Scattering Using Cr Kα Radiation

Narayanan¹,

Velmurugan²

2013

CSTA

View full text Add to dashboard Cite

High-throughput crystallography requires a method by which the structures of proteins can be determined quickly and easily. Experimental phasing is an essential technique in determining the three-dimensional protein structures using single-crystal X-ray diffraction. In macromolecular crystallography, the phases are derived either by Molecular Replacement (MR) method using the atomic coordinates of a structurally similar protein or by locating the positions of heavy atoms that are intrinsic to the protein or that have been added (MIR, MIRAS, SIR, SIRAS, MAD and SAD). Availability of in-house lab data collection sources (Cu Kα and Cr Kα radiation), cryo-crystallography and improved software for heavy atom location and density modification have increased the ability to solve protein structures using SAD. SAD phasing using intrinsic anomalous scatterers like sulfur, chlorine, calcium, manganese and zinc, which are already present in the protein becomes increasingly attractive owing to the advanced phasing methods. An analysis of successful SAD phasing on three proteins, lysozyme, glucose isomerase and thermolysin based on the signal of weak anomalous scatterers such as sulfur atom and chloride ion have been carried out. This analysis also proves that even the anomalous signal provided or present naturally in a macromolecule is good enough to solve crystal structures successfully using lab source chromium-generated X-ray radiation.

show abstract

Structure of a functional IGF2R fragment determined from the anomalous scattering of sulfur

Cited by 93 publications

References 51 publications

Insulin‐like growth factor ligands, receptors, and binding proteins in cancer

Insulin‐like growth factor ligands, receptors, and binding proteins in cancer

Tissue-Specific Inactivation of Murine M6P/IGF2R

Lab Source Anomalous Scattering Using Cr Kα Radiation

Contact Info

Product

Resources

About