Die Entfaltung der C‐terminalen α‐Helix des Neuropeptids Y ist entscheidend für die Bindung und Aktivierung des Y2‐Rezeptors
作者： Anette Kaiser , Paul Müller , Tristan Zellmann , Holger A. Scheidt , Lars Thomas
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摘要: Trotz jungster Fortschritte in der Strukturbestimmung von G-Protein-gekoppelten Rezeptoren (GPCR) gibt es nur wenige Daten zur Interaktion GPCRs mit groseren Peptidliganden. In dieser Arbeit kombinieren wir Methoden NMR-Spektroskopie, molekularen Modellierung und ortsgerichteten komplementaren Mutagenese prasentieren ein Strukturmodell des Peptidhormons Neuropeptid Y (NPY) im Komplex seinem humanen Y2-Rezeptor (Y2R). Festkorper-NMR-Messungen spezifisch isotopenmarkiertem NPY in vitro gefaltetem Phospholipid-Bizellen rekonstituiertem Y2R liefern bioaktiven Peptidstruktur. Unterstutzt Losungs-NMR-Studien konnten Interaktionen Liganden dem zweiten extrazellularen Loop Rezeptors uber hydrophobe Kontakte nachgewiesen werden. Die C-terminale α-Helix NPY, die sich einer Membranumgebung Abwesenheit bildet, entfaltet ab T 32, um einen optimalen Kontakt tief Bindungstasche transmembranen Bereichs zu ermoglichen.
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