| A HOT-SPOT OF BINDING-ENERGY IN A HORMONE-RECEPTOR INTERFACE |
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| Author(s): CLACKSON T, WELLS JA |
| Source: SCIENCE Volume: 267 Issue: 5196 Pages: 383-386 Published: JAN 20 1995 |
| Times Cited: 903 References: 43 |
| Abstract: The x-ray crystal structure of the complex between human growth hormone (hGH) and the extracellular domain of its first bound receptor (hGHbp) shows that about 30 side chains from each protein make contact. Individual replacement of contact residues in the hGHbp with alanine showed that a central hydrophobic region, dominated by two tryptophan residues, accounts for more than three-quarters of the binding free energy. This ''functional epitope'' is surrounded by less important contact residues that are generally hydrophilic and partially hydrated, so that the interface resembles a cross section through a globular protein. The functionally important residues on the hGHbp directly contact those on hGH. Thus, only a small and complementary set of contact residues maintains binding affinity, a property that may be general to protein-protein interfaces. |
| Document Type: Article |
| Language: English |
Addresses:
1. GENENTECH INC, DEPT PROT ENGN, S SAN FRANCISCO, CA 94080 USA |
| Publisher: AMER ASSOC ADVAN SCIENCE, 1333 H ST NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: QC273 |
| ISSN: 0036-8075 |