We dissected the domain of HAP2 that mediates subunit association in the heteromeric CCAAT-binding complex, first by genetic mutational analysis and then by structural studies. The mutational data suggest that a very short region in HAP2 mediates protein-protein association and that the structure of this domain is likely to be an alpha-helix. The CD analyses of a 15-residue synthetic oligopeptide covering this region confirm this surmise. The oligopeptide indeed formed an unusually thermal stable alpha-helix in aqueous solution. Eight amino acids that lie along one face of this helix, including three arginines, are found to be critical for protein-protein association. The partner that interacts with this helical motif is likely to be another subunit in the HAP complex, since the CCAAT-binding factor is shown to contain one molecule of HAP2. Our results suggest that very short regions in proteins can encode precise structures and mediate stable and specific protein-protein recognition and interactions.

• PMID: 8159696
• DOI full text
• PMC full text
• PubMed
• PubTator

Reference Type

Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, Non-P.H.S. | Research Support, U.S. Gov't, P.H.S.

Authors

Xing Y, Zhang S, Olesen JT, Rich A, Guarente L

Primary Lit For

Additional Lit For

Review For