Acetylation of Surface Lysine Groups of a Protein Alters the Organization and Composition of Its Crystal Contacts.
This paper uses crystals of bovine carbonic anhydrase (CA) and its acetylated variant to examine (i) how a large negative formal charge can be accommodated in protein-protein interfaces, (ii) why lysine residues are often excluded from them, and (iii) how changes in the surface charge of a protein can alter the structure and organization of protein-protein interfaces. It demonstrates that acetylation of lysine residues on the surface of CA increases the participation of polar residues (particularly acetylated lysine) in protein-protein interfaces, and decreases the participation of nonpolar residues in those interfaces. Negatively charged residues are accommodated in protein-protein interfaces via (i) hydrogen bonds or van der Waals interactions with polar residues or (ii) salt bridges with other charged residues. The participation of acetylated lysine in protein-protein interfaces suggests that unacetylated lysine tends to be excluded from interfaces because of its positive charge, and not because of a loss in conformational entropy. Results also indicate that crystal contacts in acetylated CA become less constrained geometrically and, as a result, more closely packed (i.e., more tightly clustered spatially) than those of native CA. This study demonstrates a physical-organic approach-and a well-defined model system-for studying the role of charges in protein-protein interactions.
Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.|Department of Applied Chemistry, Kyung Hee University , 1732 Deogyeong-daero, Giheung, Yongin, Gyeonggi 17104, Republic of Korea.
Kyungtae
K
Kang
Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
Jeong-Mo
JM
Choi
Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
Jerome M
JM
Fox
Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
Phillip W
PW
Snyder
Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
Demetri T
DT
Moustakas
Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.|Wyss Institute of Biologically Inspired Engineering, Harvard University , 60 Oxford Street, Cambridge, Massachusetts 02138, United States.
George M
GM
Whitesides
D000107:Acetylation; D000818:Animals; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D055672:Static Electricity
D002256:Carbonic Anhydrases; D008239:Lysine