PMID- 8241191 OWN - NLM STAT- MEDLINE DCOM- 19940106 LR - 20190613 IS - 0006-2960 (Print) IS - 0006-2960 (Linking) VI - 32 IP - 48 DP - 1993 Dec 7 TI - Heterodimers of the neurotrophic factors: formation, isolation, and differential stability. PG - 13350-6 AB - We have determined that all four known members of the neurotrophin family, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4), are capable of forming noncovalent heterodimers. The formation of these heterodimers was accomplished by homodimer subunit exchange promoted by treatment with guanidine hydrochloride, urea, low pH, or acetonitrile. In some cases (BDNF and mouse NGF; BDNF and NT-4), generation of the heterodimers was achieved by incubating homodimer mixtures in a neutral buffer at ambient temperature. The formation of heterodimers was in each case detected by nondenaturing gel electrophoresis at pH 7.4. High-performance cation-exchange chromatography was used to separate neurotrophin heterodimers from their parental homodimers. Heterodimers between BDNF and NT-3, BDNF and NT-4, and NT-3 and NT-4 are stable and show only a very small increase in homodimer content after 24 h of incubation at 37 degrees C. In contrast, heterodimers containing NGF subunits undergo gradual rearrangement to the homodimers. Our studies indicate that low pH, acetonitrile, and urea merely increase the neurotrophin subunit exchange rate and decrease the time needed to reach an equilibrium between a heterodimer and its two parental homodimers. FAU - Radziejewski, C AU - Radziejewski C AD - Regeneron Pharmaceuticals Inc., Tarrytown, New York 10592. FAU - Robinson, R C AU - Robinson RC LA - eng PT - Journal Article PL - United States TA - Biochemistry JT - Biochemistry JID - 0370623 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Macromolecular Substances) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurotrophin 3) RN - 0 (Recombinant Proteins) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor MH - Chromatography, Gel MH - Circular Dichroism MH - Macromolecular Substances MH - Mice MH - Molecular Weight MH - Nerve Growth Factors/*chemistry MH - Nerve Tissue Proteins/*chemistry MH - Neurotrophin 3 MH - Protein Binding MH - Protein Structure, Secondary MH - Recombinant Proteins EDAT- 1993/12/07 00:00 MHDA- 1993/12/07 00:01 CRDT- 1993/12/07 00:00 PHST- 1993/12/07 00:00 [pubmed] PHST- 1993/12/07 00:01 [medline] PHST- 1993/12/07 00:00 [entrez] AID - 10.1021/bi00211a049 [doi] PST - ppublish SO - Biochemistry. 1993 Dec 7;32(48):13350-6. doi: 10.1021/bi00211a049.