Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0271276 (Hudson)
 1,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three models have been proposed for the arrangement of proteolipid protein (PLP) in the myelin membrane. We have tested these models by determining to what extent each is consistent with the membrane-membrane interactions and electron density profile of central nervous system myelin obtained from X-ray diffraction. Equilibrium periods and membrane separations were calculated from the proposed organization of lipids and proteins in the membrane, and compared with values obtained experimentally as a function of pH and ionic strength. The orientation of the proteins was also used to calculate electron density levels in the cytoplasmic and extracellular spaces. We found that the Stoffel and Hudson models for PLP were more consistent than the Laursen model with the range of pH over which the intermembrane separation at the extracellular apposition is a minimum. The Hudson model also fits better the swollen periods observed at alkaline pH. The Hudson PLP model has many more residues in the extracellular side of the membrane than does either of the other models, resulting in higher electron density in the extracellular space compared to the cytoplasmic space. Such an asymmetric distribution of electron density is offset by the electron density of myelin basic protein which is localized in the cytoplasmic space. The resulting similar levels of electron density at the two appositions are like those in profiles calculated from the X-ray data.
 ...
PMID:Orientation of proteolipid protein in myelin: comparison of models with X-ray diffraction measurements. 247 43

Three new models for proteolipid protein (PLP) topology in the myelin membrane have been proposed--the 4-helix N(in) and N(out) models of Popot (J. Membr. Biol. 120:233-246), and the model of Weimbs and Stoffel (Biochemistry 31:12289-12296). Unlike the earlier models proposed by Laursen (Proc. Natl. Acad. Sci. USA 81:2912-2916), Stoffel (Proc. Natl. Acad. Sci. USA. 81:5012-5016) and Hudson (J. Cell Biol. 109:717-727), the four hydrophobic clusters are all assigned as membrane-spanning domains. The Popot-N(in) and Weimbs models, which are similar to the Laursen model, both assign the positively-charged domain, which is deleted from the DM20 transcript of PLP, to the cytoplasmic surface, while the Popot-N(out) model, similar to the Stoffel and Hudson models, assigns this sequence to the extracellular surface. Our calculations of membrane surface charge shows that the disposition of this basic domain greatly influences membrane interactions, by shifting the equilibrium myelin period to alkaline pH due to the electrostatic repulsion force at the extracellular apposition. In the Laursen, Popot-N(in) and Weimbs models, the onset of swelling was calculated to be at lower pH than in the Stoffel, Hudson and Popot-N(out) models, and lower than that observed experimentally with mouse optic nerve myelin. The absolute electron density profile of the myelin membrane that is derived from the x-ray diffraction patterns shows similar density levels at its cytoplasmic and extracellular surfaces. By contrast, the electron density profile calculated from a chemical model that includes lipids plus myelin basic protein (but not PLP) shows a higher density at the cytoplasmic than at the extracellular side.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Membrane topology of PLP in CNS myelin: evaluation of models. 752 56

The production of myelin by oligodendrocytes requires the coordinated, massive synthesis of myelin components, a program that is dependent on transcriptional controls. Myelin transcription factor I (MyTI) was named for its ability to recognize the proteolipid protein (PLP) gene, the most abundantly transcribed central nervous system myelin gene (Kim and Hudson: Mol. Cell Biol. 12:5632, 1992). MyTI is a zinc-dependent, DNA-binding protein of the Cys2-His-Cys class. The pattern of MyTI expression, documented in the present study, suggests that MyTI may be instrumental in early stages of oligodendrocytic development and myelin production. MyTI mRNA transcripts are more highly expressed in oligodendrocyte progenitors than in differentiated oligodendrocytes. In vitro and in vivo analyses show that MyTI immunoreactivity is stronger in oligodendrocytic progenitors than in mature oligodendrocytes which have already accumulated PLP. In oligodendrocyte progenitors, MyTI immunoreactivity appears as speckles within the nucleus, suggestive of an association of MyTI with a function that is spatially segregated into discrete nuclear domains. MyTI continues to be expressed in cells transcribing PLP. However, as oligodendrocytes accumulate PLP, MyTI immunoreactivity becomes restricted to the cytoplasm and progressively diminishes. Since MyTI has two widely separated sets of DNA-binding domains and initial MyTI expression markedly precedes PLP expression, we hypothesize the following model: MyTI may play a role in assembling transcriptionally active complexes of PLP, perhaps by bending the DNA of the promoter region to induce an appropriate conformation to enable subsequent binding of additional regulatory proteins.
 ...
PMID:Expression of myelin transcription factor I (MyTI), a "zinc-finger" DNA-binding protein, in developing oligodendrocytes. 853 Jan 87