Human Placental Lactogen
Homo sapiens (human)
Life cycle of females belonging to primates group of mammals has a possibility to have periods of pregnancy, child bearing and lactations. As such, females must developed physiological mechanisms that enable to exert such array of different behaviors and functions. There is a whole lot of hormones based regulatory loops, which are partially accountable for above mentioned physiological changes. During pregnancy and after delivery, female exerts special functions, such as fetal growth, special metabolism, and stimulating lactation, which are common to primates. How are those functions (reactions) triggered? One answer is "by hormones". Hormone is a collective term meaning signal molecules secreted by an endocrine cell into the blood-stream, which in turn carry them to distant cells. During pregnancy, placental lactogens and placental growth hormone are increasingly produced, corresponding to less production of prolactins and growth hormones. Placental lactogens, placental growth hormone, prolactins, and growth hormones are proteins that belong to the so-called cytokines. Human placental lactogens and human growth hormones are delivered to specific cells through blood-stream, and bind to extracellular domain of human prolactin receptor on the cell surface. This binding induces the receptor to dimerize, in a Zn2+ -dependent manner, triggering the reactions inside the cell, for example, milk production. Although much information about human prolactins and human growth hormones is available including cell biological, biophysical, structural, and protein engineering studies, not so much information is available about placental lactogens from human and other species.
The structure shown here is human placental lactogens. It has four-alpha helix bundles arranged in an up-up-down-down topology with two long cross-over loops which is a typical cytokine fold. As it is mentioned above, this human placental lactogen and human growth hormone bind to the same receptor, human prolactin receptor. By comparing this free state human placental lactogen with the 1:1 complex structure of human growth hormone and human prolactin receptor. two surface loops take different conformation. Moreover, several residues contribute for binding to receptor quite differently, even though those residues are identical between human placental lactogen and human growth hormone.
Protein Data Bank (PDB)
Walsh, S.T.R. Kossiakoff, A.A.; "Crystal Structure and Site 1 Binding Energetics of Human Placental Lactogen."; J.Mol.Biol.; (2006) 358:773-784 PubMed:16546209.
author: Sachiyo Nomura