Sandbox Reserved 1648: Difference between revisions
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- two CRH domains (a distal membrane homology of the first cytokine receptor '''CHR1''' and a second homology of the cytokine receptor '''CRH2''') | - two CRH domains (a distal membrane homology of the first cytokine receptor '''CHR1''' and a second homology of the cytokine receptor '''CRH2''') | ||
- an immunoglobuline-like domain ('''IGD''') | - an immunoglobuline-like domain ('''IGD ''' (<scene name='86/868181/Igd/1'>IGD heavy chain</scene> and <scene name='86/868181/Igd/2'>IGD light chain</scene>)) <ref name="refe"> Sequence and annotations Leptin Receptor-antibody complex : https://www.ncbi.nlm.nih.gov/Structure/icn3d/full.html?&mmdbid=97998&bu=1&showanno=1&source=full-feature </ref> <ref name="ref4"> Leptin : https://www.eurofins-biomnis.com/referentiel/liendoc/precis/LEPTINE.pdf </ref> | ||
- two additional membrane-proximal fibronectin type III ('''<scene name='86/868181/Fn_iii/1'>single FN III domain</scene> or <scene name='86/868181/Fn_iii/2'>Fn III domains</scene> | - two additional membrane-proximal fibronectin type III ('''FN III''' (<scene name='86/868181/Fn_iii/1'>single FN III domain</scene> or <scene name='86/868181/Fn_iii/2'>Fn III domains</scene>)) domains <ref> Structure of the Human Obesity Receptor Leptin-Binding Domain Reveals the Mechanism of Leptin Antagonism by a Monoclonal Antibody : https://doi.org/10.1016/j.str.2012.01.019 </ref> <ref name="refl"> </ref> <ref name="refe"> </ref>. | ||
ObR is heavily glycosylated causing an increase of 30-70 kDa in molecular weight <ref name="refl"> </ref> . | ObR is heavily glycosylated causing an increase of 30-70 kDa in molecular weight <ref name="refl"> </ref> . | ||
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Leptin receptors are found in different regions depending on the short or long form of the protein. | Leptin receptors are found in different regions depending on the short or long form of the protein. | ||
The '''long form''' (Ob- | The '''long form''' (Ob-Rb) is mainly present in the [https://en.wikipedia.org/wiki/Hypothalamus '''hypothalamus'''], notably in the [https://en.wikipedia.org/wiki/Arcuate_nucleus arcuate nucleus], [https://en.wikipedia.org/wiki/Dorsomedial_hypothalamic_nucleus dorsomedial] and [https://en.wikipedia.org/wiki/Ventromedial_nucleus_of_the_hypothalamus ventromedial] nuclei, and in the paraventricular nucleus ([https://en.wikipedia.org/wiki/Paraventricular_nucleus_of_hypothalamus PVN]) <ref name="ref4"> </ref> <ref name="ref5"> La leptine : votre cerveau, l'appétit et l'obésité : https://www.societe-neuroendocrinologie.fr/Breves/03-La-leptine-votre-cerveau-l-appetit-et-l-obesite </ref> <ref name="ref6"> La leptine : une clé pour la reproduction : http://www.ipubli.inserm.fr/bitstream/handle/10608/1310/1999_2_191.pdf?sequence=2 </ref>. It is also found in lesser amounts in the [https://en.wikipedia.org/wiki/Pancreatic_islets '''islets of Langerhans'''] in mice, as well as in the '''liver''', '''spleen''', '''heart''', [https://en.wikipedia.org/wiki/White_adipose_tissue '''white fat'''], [https://en.wikipedia.org/wiki/Lymph_node '''lymph node'''], [https://en.wikipedia.org/wiki/Jejunum '''jejunum'''] and [https://en.wikipedia.org/wiki/Hematopoietic_stem_cell '''hematopoietic stem cells''']<ref name="ref2"/> <ref name="ref7"> Hormonal Regulation of Fuel Metabolism : https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/leptin-receptor </ref>. | ||
The '''short-form''' (Ob-Ra) is located primarily in the '''lungs''', '''kidneys''' and '''islets of Langerhans''' <ref name="ref4"/>. It is also present in smaller quantities in the brain at the '''hypothalamus'''.<ref name="ref5"/> Ob-Ra is the only form of the protein found in '''ovaries'''. Short form facilitates the passage of leptin across the blood cerebrospinal fluid barrier. | The '''short-form''' (Ob-Ra) is located primarily in the '''lungs''', '''kidneys''' and '''islets of Langerhans''' <ref name="ref4"/>. It is also present in smaller quantities in the brain at the '''hypothalamus'''.<ref name="ref5"/> Ob-Ra is the only form of the protein found in '''ovaries'''. Short form facilitates the passage of leptin across the blood cerebrospinal fluid barrier. | ||
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The '''CRH2''' domain is the main leptin binding site on the receptor. This domain is required for the activation of the receptor. It is composed of a region of four consecutive hydrophobic residues. In particular, <scene name='86/868181/Leu_13/1'>Leu13</scene> and <scene name='86/868181/Leu_86/1'>Leu86</scene> of leptin interact with '''<scene name='86/868181/Leu_504/2'>Leu504</scene>''' in CRH2 forming a bond via hydrophobic interactions<ref>Mapping of the interface between leptin and the leptin receptor CRH2 domain : https://jcs.biologists.org/content/118/11/2519 </ref>. In contrast, the receptor functionality is hardly affected when the CRH1 domain is deleted. | The '''CRH2''' domain is the main leptin binding site on the receptor. This domain is required for the activation of the receptor. It is composed of a region of four consecutive hydrophobic residues. In particular, <scene name='86/868181/Leu_13/1'>Leu13</scene> and <scene name='86/868181/Leu_86/1'>Leu86</scene> of leptin interact with '''<scene name='86/868181/Leu_504/2'>Leu504</scene>''' in CRH2 forming a bond via hydrophobic interactions<ref>Mapping of the interface between leptin and the leptin receptor CRH2 domain : https://jcs.biologists.org/content/118/11/2519 </ref>. In contrast, the receptor functionality is hardly affected when the CRH1 domain is deleted. | ||
The '''IGD''' domain has no affinity for leptin but is nevertheless '''required''' for receptor activation. In the absence of this domain, the result is a receptor with a wild-type affinity for leptin. However, the receptor is completely devoid of biological activity. | The '''IGD''' (<scene name='86/868181/Igd/1'>IGD heavy chain</scene> and <scene name='86/868181/Igd/2'>IGD light chain</scene>) domain has no affinity for leptin but is nevertheless '''required''' for receptor activation. In the absence of this domain, the result is a receptor with a wild-type affinity for leptin. However, the receptor is completely devoid of biological activity <ref name="refe"> </ref> . | ||
In the '''<scene name='86/868181/Fn_iii/1'>FN III</scene>''' domains, there are two conserved '''cysteines''' ('''Cys-672 and Cys-751''' <ref>Leptin receptor activation depends on critical cysteine residues in its fibronectin type III subdomains : https://www.jbc.org/article/S0021-9258(20)61429-6/fulltext </ref>) that are crucial for the activation of the receptor. | In the '''<scene name='86/868181/Fn_iii/1'>FN III</scene>''' domains, there are two conserved '''cysteines''' ('''Cys-672 and Cys-751''' <ref>Leptin receptor activation depends on critical cysteine residues in its fibronectin type III subdomains : https://www.jbc.org/article/S0021-9258(20)61429-6/fulltext </ref>) that are crucial for the activation of the receptor <ref name="refe"> </ref>. | ||
Moreover, in order to form an '''<scene name='86/868181/Activated_leptin_obr_complex/1'>activated 2:4 leptin:ObR complex</scene>'''., the leptin clusters '''two pre-formed ObR dimers'''. | Moreover, in order to form an '''<scene name='86/868181/Activated_leptin_obr_complex/1'>activated 2:4 leptin:ObR complex</scene>'''., the leptin clusters '''two pre-formed ObR dimers'''. | ||
