Duplication of the MID1 first exon in a patient with Opitz G/BBB syndrome

Winter, Jennifer; Lehmann, Tanja; Suckow, Vanessa; Kijas, Zofia; Kulozik, Andreas E.; Kalscheuer, Vera M.; Hamel, B.C.J.; Devriendt, Koen; Opitz, John M.; Lenzner, Steffen; Ropers, Hans‐Hilger; Schweiger, Susann

doi:10.1007/s00439-002-0901-5

Cited by 23 publications

(29 citation statements)

References 11 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2A). Signals for the intraresidue HN to 13 Ca and 13 Cb correlations are stronger in intensity than those for the preceding residues. As a result, the partner CBCACONH spectrum, which shows only correlations to the preceding residues, is not necessary.…”

Section: Nmr Assignments Of the Mid1 Cos Domainmentioning

confidence: 80%

“…The backbone 1 H, 15 N, 13 Ca, 13 Cb, and 13 CO NMR resonances are assigned using the HNCACB and HNCO triple-resonance spectra. Good sequential amino acid connectivity is identified using the HNCACB spectrum, which shows correlations between the HN proton and 13 Ca and 13 Cb atoms of the intra-and preceding residue ( Fig. 2A).…”

Section: Nmr Assignments Of the Mid1 Cos Domainmentioning

confidence: 99%

“…As a result, the partner CBCACONH spectrum, which shows only correlations to the preceding residues, is not necessary. Figure 2A shows the NH to 13 Ca/ 13 Cb correlations for residues Phe359 to Ser367 (helix II) in which the intra-and inter-residue 13 Ca/ 13 Cb resonances are readily identifiable based on their intensities, making assignments straightforward. The CC(CO)NH spectrum, which shows NH to sidechain carbon correlations of the preceding residues, is used to not only identify amino acid type but also to resolve overlapping 13 Ca and 13 Cb signals for sequential residues when necessary ( Fig.…”

Section: Nmr Assignments Of the Mid1 Cos Domainmentioning

confidence: 99%

“…Mutations of MID1 are associated with X-linked Opitz G/BBB syndrome (XLOS), which is characterized by ventral midline abnormalities that includes cleft lip/palate, hyperspadias, and hypertelorism [2,[9][10][11][12][13]. Mutations within the C-terminal half of MID1 have been shown to result in MID1-forming cytoplasmic 'clumps' or aggregates instead of associating with the microtubules [8,14,15].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Solution structure of the microtubule‐targeting COS domain of MID1

Wright

Dagnachew

et al. 2016

The FEBS Journal

View full text Add to dashboard Cite

The human MID1 protein is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. MID1 associates with the microtubules and functions as an ubiquitin E3 ligase, targeting protein phosphatase 2A for ubiquitin-mediated regulation. The mechanism of microtubule association is not known. Recently, a 60-amino acid region termed the C-terminal subgroup One Signature (COS) box/domain was identified at the C-terminal end of the coiled-coil (CC) domain that facilitates microtubule localization. Insertion of the MID1 COS domain at the C-terminal end of the CC domain of a nonmicrotubule-associated TRIM protein confers microtubule localization. Here, we report the solution structure of the COS domain of MID1. The domain adopts a helix-loophelix structure in which the N-and C-terminal ends are in close proximity. Hydrophobic residues stabilizing the interaction of the two a-helices form a central hydrophobic core. The loop separating the a-helices is structured, with two of its hydrophobic residues making contact with the central core. On the outer surface, positively charged residues form a distinct basic patch near the termini that we postulate is important for microtubule binding. A model of the structure of the preceding coiled-coil and COS domains (CC-COS) show that the COS domain forms a helical bundle at the C-terminal end of the CC domain similar to the spectrin-like fold observed with some known microtubule-binding proteins. Interestingly, the CC-COS domains bind to microtubules, demonstrating for the first time that MID1 can directly associate with the microtubules.

show abstract

Section: Nmr Assignments Of the Mid1 Cos Domainmentioning

confidence: 80%

Section: Nmr Assignments Of the Mid1 Cos Domainmentioning

confidence: 99%

Section: Nmr Assignments Of the Mid1 Cos Domainmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Solution structure of the microtubule‐targeting COS domain of MID1

Wright

Dagnachew

et al. 2016

The FEBS Journal

View full text Add to dashboard Cite

show abstract

“…Mutations of MID1 are associated with X-linked Opitz G Syndrome (XLOS), which is characterized by cleft lip/palate, hypertelorism and hyperspadias [2], [29], [30], [31], [32]. Within the Bbox1 domain, residue Ala130 is mutated to a threonine or valine, and the cysteine residues at positions 142 and 145 are mutated to serine and threonine (Cys142Ser, and Cys145Thr), respectively.…”

Section: Introductionmentioning

confidence: 99%

XLOS-Observed Mutations of MID1 Bbox1 Domain Cause Domain Unfolding

Wright

Babatunde

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

MID1 catalyzes the ubiquitination of the protein alpha4 and the catalytic subunit of protein phosphatase 2A. Mutations within the MID1 Bbox1 domain are associated with X-linked Opitz G syndrome (XLOS). Our functional assays have shown that mutations of Ala130 to Val or Thr, Cys142 to Ser and Cys145 to Thr completely disrupt the polyubiquitination of alpha4. Using NMR spectroscopy, we characterize the effect of these mutations on the tertiary structure of the Bbox1 domain by itself and in tandem with the Bbox2 domain. The mutation of either Cys142 or Cys145, each of which is involved in coordinating one of the two zinc ions, results in the collapse of signal dispersion in the HSQC spectrum of the Bbox1 domain indicating that the mutant protein structure is unfolded. Each mutation caused the coordination of both zinc ions, which are ∼13 Å apart, to be lost. Although Ala130 is not involved in the coordination of a zinc ion, the Ala130Thr mutant Bbox1 domain yields a poorly dispersed HSQC spectrum similar to those of the Cys142Ser and Cys145Thr mutants. Interestingly, neither cysteine mutation affects the structure of the adjacent Bbox2 domain when the two Bbox domains are engineered in their native tandem Bbox1-Bbox2 protein construct. Dynamic light scattering measurements suggest that the mutant Bbox1 domain has an increased propensity to form aggregates compared to the wild type Bbox1 domain. These studies provide insight into the mechanism by which mutations observed in XLOS affect the structure and function of the MID1 Bbox1 domain.

show abstract

Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1 mutations

Suckow

Kijas

et al. 2004

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

Opitz syndrome (OS; MIM 145410 and MIM 300000) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal (LTE) abnormalities, imperforate anus, developmental delay, and cardiac defects. The X-linked form (XLOS) is caused by mutations in the MID1 gene, which encodes a microtubule-associated RBCC protein. In this study, phenotypic manifestations of patients with and without MID1 mutations were compared to determine genotype-phenotype correlations. We detected 10 novel mutations, 5 in familial cases, 2 in sporadic cases, and 3 in families for whom it was not clear if they were familial or sporadic. The genotype and phenotype was compared for these 10 families, clinically diagnosed OS patients found not to have MID1 mutations, and 4 families in whom we have previously reported MID1 mutations. This combined data set includes clinical and mutation data on 70 patients. The XLOS patients with MID1 mutations were less severely affected than patients with MID1 mutations reported in previous studies, particularly in functionally significant neurologic, LTE, anal, and cardiac abnormalities. Minor anomalies were more prevalent in patients with MID1 mutations compared to those without mutations in this study. Female MID1 mutation carriers had milder phenotypes compared to male MID1 mutation carriers, with the most common manifestation being hypertelorism in both sexes. Most of the anomalies found in the patients of the present study do not correlate with the MID1 mutation type, with the possible exception of LTE malformations. This study demonstrates the wide spectrum of severity and manifestations of OS. It also shows that XLOS patients with MID1 mutations may be less severely affected than indicated in prior reports.

show abstract

Duplication of the MID1 first exon in a patient with Opitz G/BBB syndrome

Cited by 23 publications

References 11 publications

Solution structure of the microtubule‐targeting COS domain of MID1

Solution structure of the microtubule‐targeting COS domain of MID1

XLOS-Observed Mutations of MID1 Bbox1 Domain Cause Domain Unfolding

Mild phenotypes in a series of patients with Opitz GBBB syndrome with MID1 mutations

Contact Info

Product

Resources

About