1Z7C

Crystal Structure of Human Placental Lactogen

1Z7C の概要

• エントリーDOI: 10.2210/pdb1z7c/pdb
• 分子名称: Chorionic somatomammotropin hormone (2 entities in total)
• 機能のキーワード: four-helix bundle protein, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22335.14

構造登録者

Walsh, S.T.R.,Kossiakoff, A.A. (登録日: 2005-03-24, 公開日: 2006-03-07, 最終更新日: 2024-11-20)

主引用文献

Walsh, S.T.R.,Kossiakoff, A.A.
Crystal Structure and Site 1 Binding Energetics of Human Placental Lactogen.
J.Mol.Biol., 358:773-784, 2006

PubMed Abstract: In primates, placental lactogen (PL) is a pituitary hormone with fundamental roles during pregnancy involving fetal growth, metabolism, and stimulating lactation in the mother. Human placental lactogen (hPL) is highly conserved with human growth hormone (hGH) and both hormones bind to the hPRLR extracellular domain (ECD), the first step in receptor homodimerization, in a Zn2+-dependent manner. A modified surface plasmon resonance method was developed to measure the kinetics for hPL and hGH binding to the hPRLR ECD, with and without Zn2+ and showed that hPL has about a tenfold higher affinity for the hPRLR ECD1 than hGH. The crystal structure of the free state of hPL has been determined to 2.0 A resolution showing the molecule possesses an overall structure similar to other long chain four-helix bundle cytokines. Comparison of the free hPL structure with the 1:1 complex structure of hGH bound to the hPRLR ECD1 suggests that two surface loops undergo conformational changes >10 A upon binding. An 18 residue Ala-scan was used to characterize the binding energy epitope for the site 1 interface of hPL. Individual alanine substitutions at five positions reduced binding affinity by a DeltaDeltaG > or = 3 kcal mol(-1). A comparison of the hPL site 1 epitope with that previously determined for hGH indicates contributions of individual residues track reasonably well between hPL and hGH. In particular, residues involved in the zinc-binding site and Lys172 constitute the principal binding determinants for both hormones. However, several residues that are identical between hPL and hGH contribute quite differently to the binding of the hPRLR ECD1. Additionally, the overall magnitudes of the DeltaDeltaG changes observed from the Ala-scan of hPL were markedly larger than those determined in the comparative scan of hGH to the hPRLR ECD1. The structural and biophysical data presented here show that subtle changes in the structural context of an interaction can lead to significantly different effects at the individual residue level.

PubMed: 16546209
DOI: 10.1016/j.jmb.2006.02.038

実験手法

X-RAY DIFFRACTION (2 Å)