University:
Amherst College
Course:
BIOL 191 | Molecules, Genes and Cells
Academic year:

2010
Views:

6

Pages:

25
Author:

powergirls13zhb

Cell Communica,on III: Steroid Hormones Cell Communica,on Review • Small Molecules – Example molecule? – What are its chemical characteris,cs? • Pep,des and Proteins – Example hormone? – Characteris,cs of this pep,de hormone? Cell Communica,on Review II • How do these signals get around? Steroid Hormones • Diﬀerent class of hormone – Structure – Transport – Receptors – Func,on – Estrogen will be the model steroid hormone for this lecture – Contrast to Insulin and NO Derived from Cholesterol Steroid Hormones • Generally: – Considered small molecules – Very similar chemical structures – Fundamentally ____________________ Consequences of Hydrophobic Hormones • Solubility in water? • Solubility in lipid membrane? • How does this aﬀect its transporta,on in blood? Steroid Hormones catch a ride on Carrier Proteins How are receptors diﬀerent? Basic Nuclear Receptor Ac,va,on Lets get speciﬁc: The Estrogen Receptor • A nuclear receptor • Binds Estrogen and aﬀects DNA transcrip,on • Changes paWern of gene expression • Aﬀect on organism is slow (minutes to days) Nuclear Receptor Subfamily Yellow shows the highly variable ac,va,on domain Blue shows the highly conserved DNA binding domain-‐ ~66 amino acids Red shows the hormone binding domain estrogen receptor glucocor,coid receptor Estrogen Receptor: Ligand Bound PDB # 1A52 Addi,onal views Estrogen Bound to receptor Hydrogen Bonds Hydrophobic Contacts Estrogen bound to Ligand binding domain • Deep pocket • Speciﬁc H-‐bonds • Very Hydrophobic PDB # 1A52 Binding Triggers Ac,vity • How could this happen? • We know: – Only ac,ve when __________ – One estradiol per ER monomer – Forms dimers – Ligand binding domain is connected to DNA binding domain (Not shown yet) DNA Binding Domain • Zn ﬁnger • >700 genes include this fold • Zif268, a classic Zn ﬁnger is shown here • The _____ interacts with the DNA Steroid Receptors use Zn ﬁngers • Structural mo,f is highly versa,le • Proteins can have 1 to 37 of these ﬁngers • More ﬁngers, longer DNA sequence recognized • Recogni,on is based of non-‐ covalent, complementarity between amino acids on helix and base pair sequence of DNA Steroid receptors recognize related DNA sequences ER DNA binding domain PDB 1HCQ Un-‐natural Signaling? • Non-‐natural non-‐steroidal ligands • Environmental Estrogens – ____________: from plants but remember plants don’t have cholesterol so must be non-‐steroidal pathways to deriva,ves. – _____________: “Other” estrogens • DDT (the most potent estrogenic mimic known, much stronger than estrogen) • Bisphenol A – Nalgen recalled its plas,c water boWles due to this compound

Cell Communication III Steroid Hormones

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